bmj open€¦ · provided updated recommendations on lipid-modifying therapy (lmt) for...

For peer review only

Implications of the National Institute for Health and Care

Excellence (NICE) 2014 Lipid Modification Guidelines to

Contemporary UK Practice

Journal: BMJ Open

Manuscript ID bmjopen-2016-013255

Article Type: Research

Date Submitted by the Author: 30-Jun-2016

Complete List of Authors: Steen, Dylan; University of Cincinnati College of Medicine, Division of CV Health and Disease, UC Heart, Lung, and Vascular Institute, University of Cincinnati College of Medicine

Khan, Irfan; Sanofi, Global Health Economics and Outcomes Research Ansell, David; IMS Health Sanchez, Robert; Regeneron Pharmaceuticals Inc. , Global Health Economics and Outcomes Research Ray, Kausik; Imperial College London, Department of Primary Care and Public Health

<b>Primary Subject Heading</b>:

Cardiovascular medicine

Secondary Subject Heading: Cardiovascular medicine

Keywords: low-density lipoprotein cholesterol (LDL-C), lipids, guidelines, cardiovascular disease, statins

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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Implications of the National Institute for Health and Care

Excellence (NICE) 2014 Lipid Modification Guidelines to

Contemporary UK Practice

Dylan Steen,1 Irfan Khan,2 David Ansell,3 Robert J. Sanchez,4 Kausik K. Ray5

1Division of Cardiovascular Health and Disease, University of Cincinnati College of

Medicine, Cincinnati, OH, USA

2Global Health Economics and Outcomes Research, Sanofi, Bridgewater, NJ, USA

3IMS Health, London, UK

4Global Health Economics and Outcomes Research, Regeneron Pharmaceuticals Inc.,

Tarrytown, NY, USA

5Department of Primary Care and Public Health, Imperial College, London, UK

Correspondence to:

Dylan Steen

Director of Clinical Trials and Population Health Research

Division of CV Health and Disease

UC Heart, Lung, and Vascular Institute, University of Cincinnati College of Medicine

Cardiovascular Center, 231 Albert Sabin Way, Cincinnati, OH 45267

Tel: (513) 558-6573; Fax: (513) 558-4545; Email: [email protected]

Word count: 3799 (main body of the article)

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What this Paper Adds

In 2014, guidelines from the National Institute for Health and Care Excellence (NICE)

provided updated recommendations on lipid-modifying therapy (LMT) for cardiovascular

(CV) event risk reduction. In contrast to prior guidelines which advocated a cholesterol

target based approach for those at risk of CV disease, these latest guidelines moved

towards an approach focused on the intensity of statin therapy. The potential

implications of these changes on current UK practice have not been evaluated in prior

reports. Furthermore, our study also provides novel data on clinical practice in many

high-risk subgroups such as those with ischaemic stroke, diabetes without vascular

disease, and chronic kidney disease, which have not been compared in previous

reports.

Our findings suggest that approximately 94% of patients with vascular disease and 85%

of high-risk non-vascular disease patients, representing approximately 3 million

individuals in each of these groups, will require either statin up-titration or initiation in

order to comply with NICE 2014 guidelines. The impact of this additional workload on

medical resources, costs and patient compliance with new lipid lowering regimens is

unclear.

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ABSTRACT

Background: In 2014, guidelines from the National Institute for Health and Care

Excellence (NICE) provided updated recommendations on lipid-modifying therapy

(LMT). We assessed clinical practice relative to these guidelines in a contemporary UK

general-practice setting for secondary and high-risk primary-prevention populations, and

extrapolated the findings to UK nation-level.

Methods: Patients from The Health Improvement Network database with the following

criteria were included: lipid profile in 2014 (index date); ≥20 years of age; ≥2 years

representation in database prior to index date; and ≥1 statin indication either for

atherosclerotic cardiovascular disease (ASCVD) or the non-ASCVD conditions of high-

risk diabetes mellitus and/or chronic kidney disease.

Results: Overall, 183565 patients met the inclusion criteria (n=91479 for ASCVD and

92086 for non-ASCVD). In those with ASCVD, 79% received statin treatment and 31%

received a high-intensity statin. In the non-ASCVD group, 62% were on a statin and

57% received medium- or high-intensity statin. In the ASCVD and non-ASCVD cohorts,

only 6% and 15%, respectively, were treated according to dosing recommendations as

per the updated NICE guidelines. Extrapolation to the 2014 UK population indicated

that, of the 3.3 million individuals with ASCVD, 2.4 million would require statin up-

titration and 680000 would require statin initiation (31% de-novo initiation, 60% re-

initiation, 9% potential add-on to non-statin LMT). Similarly, of the 3.5 million high-risk

non-ASCVD individuals, 1.6 million would require statin up-titration and 1.4 million

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would require statin initiation (59% de-novo initiation, 36% re-initiation, 5% potential

add-on to non-statin LMT).

Conclusions: Although a large proportion of UK individuals with ASCVD and high-risk

non-ASCVD receive statin treatment (79% and 62%, respectively), considerable gaps

remain relative to updated recommendations. Approximately 94% of ASCVD patients

and 85% of high-risk non-ASCVD individuals, representing approximately 3 million

individuals in each group, would require either statin up-titration or initiation to comply

with NICE 2014 guidelines.

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Strengths and limitations of this study

� Implications of changes to NICE guidelines on lipid-modifying therapy in 2014 on

clinical practice in UK have not been evaluated in prior reports

� We developed a cohort high-risk patients representing the UK general practice from

a large representative data source and developed estimates of the extrapolated

number of individuals across the UK, within several groups of interest, whose

treatment was compliant with the new guidelines and those for whom up-titration or

initiation of statin therapy would be needed

� Our study also provides novel data on clinical practice in many high-risk subgroups

such as those with ischaemic stroke, diabetes without vascular disease, and chronic

kidney disease, which have not been compared in previous reports

� A limitation of the study is that the summary demographic and clinical characteristics

of the cohort were based on information available in the database; certain data such

as body-mass index, ethnicity, blood pressure, and smoking status were not

available for all patients

� Another limitation of the study is that though the definition of medication utilisation

was optimised to provide valid point-in-time estimates concurrent with lipid

measurements, whether patients actually took their medications as prescribed

cannot be ensured from the data source

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Introduction

Despite a decade of continuing decline in cardiovascular (CV) disease mortality, CV

deaths remain the leading cause of mortality in the UK, accounting for approximately

31% of all deaths, with ischaemic heart disease and stroke representing the vast

majority (17% and 10%, respectively).1,2 Reducing low-density lipoprotein cholesterol

(LDL-C) with statin therapy has been shown to reduce all-cause and CV mortality, as

well as CV outcomes such as non-fatal myocardial infarction (MI), coronary

revascularisation procedures, and non-fatal ischaemic stroke in populations with prior

atherosclerotic CV disease (ASCVD) and in certain primary-prevention populations.3,4

The high tolerability and safety of statins have also been established across these

subgroups.3-5 Despite this, appropriate statin use and atherogenic lipid level reduction

remain suboptimal in clinical practice.6

Statins are recommended by the National Institute for Health and Care Excellence

(NICE) as first-line lipid modifying therapy (LMT) for the reduction of CV events in

patients with ASCVD as well as diabetes mellitus (DM), familial hypercholesterolaemia,

chronic kidney disease (CKD), and other high-risk primary-prevention populations.7 In

line with evidence from randomised trials and the recent availability of generic

atorvastatin, the 2014 NICE guidelines recommend more intensive statin therapy

compared to the 2008 guidelines. The recommended regimens include atorvastatin 80

mg for patients with ASCVD and atorvastatin 20 mg or higher for those with most other

high-risk conditions.

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The present study assessed clinical practice in 2014 relative to the updated NICE

guidelines. In a large, representative UK population, we analysed LMT utilisation for

each of the following indications: recent acute coronary syndrome (ACS), other

coronary heart disease (CHD), ischaemic stroke / transient ischaemic attack (TIA),

peripheral arterial disease (PAD), type 1 (T1) DM, type 2 (T2) DM, and CKD. We

provide an estimate of the extrapolated number of individuals in the UK within each

subgroup whose treatment was compliant with the guidelines as well as those for whom

up-titration or initiation of statin therapy would be needed. For the same patient

subgroups, we also evaluated achievement of LDL-C and non-high-density lipoprotein

cholesterol (non-HDL-C) goals as defined by the 2011 European Society of Cardiology

(ESC) / European Atherosclerosis Society (EAS) lipid management guidelines.8

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Methods

This study was based on a retrospective, cross-sectional, and observational cohort. It

was approved by the Scientific Review Committee, an independent UK-based ethics

committee established to review studies from The Health Improvement Network (THIN).

Database and cohort selection

We utilised the THIN database, which represents anonymised patient records from

general practitioners (GPs) in the UK. As of the end of 2014, the database represented

422 active GP practices and 3.5 million unique active patients. The THIN database has

been found to be broadly representative of the UK population, and the validity of

recorded information has been established in previous studies,9,10 including the validity

of utilising Read codes to identify ASCVD, other high CV risk conditions, and incident

CV events.11,12 Due to the extensive use of GP electronic prescribing in the UK, the

recording of prescriptions is expected to be both complete and accurate.13 Furthermore,

the scope of THIN data to inform complex epidemiological observations was supported

by the validation of the updated QRISK2 model for estimating the 10-year incident risk

of CV disease in the UK general population.14

The following inclusion criteria were utilised: presence of a lipid profile

measurement in 2014 (last LDL-C measurement in 2014 was considered the index

date); ≥20 years of age; and presence of ≥1 high CV risk condition for which statins

would be recommended as per NICE guidelines (see below). In order to ensure

complete capture of pertinent demographic and clinical characteristics, and to assess

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for prior statin use among those not currently treated with statins, we also required

continuous representation in the database for ≥2 years prior to the index date.

High CV risk conditions were identified using standardised Read codes (see

supplemental table S1) as follows: 1) recent ACS (MI or unstable angina within 12

months prior to index date); 2) other CHD (e.g. ACS >12 months prior to index date, any

coronary revascularisation, stable angina, or ischaemic cardiomyopathy); 3) ischaemic

stroke or TIA; 4) PAD (presence of revascularisation/surgery for significant peripheral

artery, aortic, or carotid disease); 5) T2DM with QRISK2 10-year risk ≥10%; 6) T1DM

with age >40 years; and 7) CKD stage III-V (estimated glomerular filtration rate <60

mL/min/1.73 m2 or dialysis, herewith referred to as “CKD”). A thorough process

involving clinical cardiology and coding expert review was undertaken to optimise the

specificity of Read codes for each condition. Read codes were also used to identify non-

CV comorbidities. The QRISK2 10-year risk was estimated for individuals with T2DM in

the non-ASCVD cohort via application of algorithm to patient-level data.14

Patients with conditions 1-4 were collectively referred to as “ASCVD”, while those

with only conditions 5-7 were collectively referred to as “non-ASCVD”. Those with

ASCVD were categorised hierarchically (as above) into four mutually exclusive groups:

1) recent ACS; 2) other CHD; 3) ischaemic stroke/TIA; and 4) PAD. A sensitivity

analysis was also conducted by categorising these same patients by each condition

present, referred to as prevalent disease categorisation. As an example, an individual

with a history of elective coronary revascularisation and PAD would be categorised

hierarchically as “other CHD,” but as both “other CHD” and “PAD” under the prevalent

disease categorisation. Non-ASCVD patients were categorised into five mutually

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exclusive categories to better evaluate the association of specific conditions with LMT

utilisation and lipid goal achievement. These categories were: 1) T2DM and QRISK2

≥10% with CKD; 2) T2DM and QRISK2 ≥10% without CKD; 3) T1DM and age >40

years with CKD; 4) T1DM and age >40 years without CKD; and 5) other CKD not

meeting the criteria of the other categories. In order to abbreviate summary findings,

further identification of the first four categories will omit the qualifiers QRISK2 ≥10% and

age >40 years, considering them implicit in the definitions. The fifth category will be

referred to as “CKD alone”.

Determination of medication treatment

For any particular medication, patients were considered to have been treated on the

index date if the medication supply via a recorded prescription was present on or within

30 days prior to the index date, regardless of the duration of the prescription (fig 1). This

point-in-time assessment approach was utilised to better control for factors such as

discontinuation over time in summarising treatment patterns as of index date. In

addition, this also ensured that lipid levels best reflected the impact of the treatment

regimen as the assessment of both measures was concurrent. Those not treated on the

index date but with evidence of a prior recorded prescription were considered to have a

history of being treated. Those without any evidence of a recorded prescription for a

medication within the 2 years prior to the index date were considered to have no

documented history of being treated. LMT was categorised as high-, medium-, and low-

intensity statin therapy, as well as non-statin therapy (supplemental table S2).7 We also

summarised statin utilisation by NICE guideline recommendations, which recommend

treatment with atorvastatin 80 mg and 20 mg in ASCVD and non-ASCVD patients,

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respectively (for our study we interpreted this as regimens of equivalent or higher

potency: atorvastatin 80 mg equivalent or higher [atorvastatin 80 mg, rosuvastatin 40

mg]; and atorvastatin 20 mg equivalent or higher [atorvastatin 20, 40 and 80 mg,

rosuvastatin 10, 20 and 40 mg, and simvastatin 80 mg]). Statin categories included

statins administered as either monotherapy or in combination with ≥1 non-statin

medications.

Determination of LDL-C and non-HDL-C levels

We assessed the achievement of LDL-C and non-HDL-C levels relative to the ESC/EAS

2011 guidelines. They recommend goals of LDL-C <1.8 mmol/L (70 mg/dL) and non-

HDL-C <2.6 mmol/L (100 mg/dL) for both the ASCVD and non-ASCVD populations

reported in the current study.8

Patient Involvement

Our study was based on an analysis of patient-level data represented in an electronic

medical record (EMR) database utilized by a set of GPs in UK utilizing the Vision EMR

software. In order to protect patient privacy, the analyses reported in our study are

based on de-identified version of the database where patient identifiers are encrypted

such that it is not possible to link an individual patient in the dataset to a specific

individual in the real-world. As such, our study did not involve any direct patient-level

interaction.

Statistical analyses

All statistical analyses were descriptive in nature. Cohort characteristics, LMT utilisation,

and achieved LDL-C and non-HDL-C levels were summarised via proportions and mean

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± standard deviation (SD) as appropriate. Findings on number of patients treated with

LMT were extrapolated to the UK population via an adjusted extrapolation methodology

that accounted for differential weights by clinical and demographic profiles (details

available in Supplementary Appendix). All analyses were conducted with SAS® software

version 9.4.

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Results

The inclusion criteria were met by 183 565 patients, of whom approximately one-half

(n=91 479) had established ASCVD, with the remainder (n=92 086) having non-ASCVD

high-risk conditions (fig 2). According to hierarchical disease categorisation for the

ASCVD group, 3% had a recent ACS, 64% had another CHD diagnosis, 22% had a

history of ischaemic stroke/TIA, and 11% had PAD. Approximately one-third of the

ASCVD cohort had concomitant DM; and close to one-fourth had concomitant CKD.

Baseline characteristics of the ASCVD group by hierarchical categorisation are

presented in table 1 and by prevalent categorisation in supplemental table S3. Baseline

characteristics for the non-ASCVD group are also presented in table 1. In the non-

ASCVD group, 12% had T2DM with CKD; 57% had T2DM without CKD; 1% had T1DM

with CKD; 5% had T1DM without CKD; and 25% had CKD alone.

Current utilisation of LMT

ASCVD population

Approximately 79% of the ASCVD population received treatment with a statin on the

index date (table 2). By hierarchical categories, statin use was 87% in the recent ACS

group, 82% in the other CHD group, and 73% in both the ischaemic stroke/TIA and PAD

groups. Of patients currently treated with statins, 40% were receiving treatment with

high-intensity statins (defined as per supplementary table S2): 72% for recent ACS,

42% for other CHD, 32% for PAD, and 29% for ischaemic stroke/TIA. Statins were

predominantly used as monotherapy: 92% for high-intensity statins, 98% for medium-

intensity statins, and 96% for low-intensity statins. Of patients not currently treated with

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LMT, 34% had no evidence of any LMT treatment in the 2 years prior to the index date.

LMT utilisation by prevalent categorisation in the ASCVD group is presented in

supplemental table S4.

Non-ASCVD population

In the non-ASCVD population, 62% received treatment with a statin on the index date

(table 2). In the subgroups, statin use was 71% in T2DM with CKD, 66% in T2DM

without CKD, 73% in the T1DM with CKD, 62% in T1DM without CKD, and 49% in CKD

alone. Of the patients receiving statins, at least a medium-intensity statin was utilised in

92%. As with ASCVD patients, statins were most commonly used as monotherapy: 93%

for high-intensity statins and 98% for both medium- and low-intensity statins. Of patients

not currently treated with LMT, 62% had no evidence of any LMT treatment in the 2

years prior to the index date.

Concordance with NICE recommendations and extrapolation to the UK population

ASCVD population

Statin treatment compliant with the NICE 2014 guidelines (atorvastatin 80 mg equivalent

or higher; which is a subset of statins regarded as high-intensity) was observed in 6% of

the ASCVD cohort, with 73% treated with a less-intensive statin regimen than

recommended and 21% not treated with any statin (table 3). Extrapolated to the UK

ASCVD population, this identified approximately 202 000 individuals whose treatment

was compliant with the updated guidelines, 2.4 million who would require statin up-

titration, and 680 000 in whom statin initiation would be recommended. For those

requiring statin initiation, 31% represented a need for de-novo initiation, 60% re-

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initiation due to past discontinuation, and 9% potential statin add-on to non-statin LMT.

NICE-recommended statin therapy was most commonly used in patients with a recent

ACS (33%) and the least used in patients with history of an ischaemic stroke/TIA or

PAD (2% each).


Statin treatment compliant with the NICE 2014 guidelines (atorvastatin 20mg equivalent

or higher) was observed in 15% of the non-ASCVD cohort, with 47% treated with a less-

intensive statin regimen than recommended and 37% not treated with any statin (table

3). Extrapolation identified approximately 508 000 UK non-ASCVD patients (i.e. fulfilling

the DM and/or CKD indications) whose treatment was already compliant with the

updated guidelines, 1.6 million who require up-titration, and 1.4 million in whom statin

initiation would be recommended. For those requiring statin initiation, 59% represented

a need for de-novo initiation, 36% re-initiation due to past discontinuation, and 5%

potential statin add-on to non-statin LMT. Of the subgroups, T1DM with CKD was most

likely to already be receiving NICE-recommended statin therapy (26%) and CKD alone

was least likely (10%).

ESC/EAS-recommended lipid goal achievement

ASCVD population

The mean LDL-C was 2.3 mmol/L with approximately 31% achieving a LDL-C <1.8

mmol/L. Mean non-HDL-C was 2.9 mmol/L with approximately 42% achieving a non-

HDL-C <2.6 mmol/L. Supplemental tables S5 and S6 provide a detailed summary of the

mean LDL-C and non-HDL-C levels, achievement of LDL-C <1.8 mmol/L and non-HDL-

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C <2.6 mmol/L, by LMT treatment for prevalent and hierarchical subgroups.

Achievement of LDL-C and non-HDL-C goals was associated with the hierarchy of

ASCVD subgroups, with recent ACS being the highest and PAD being the lowest.

Patients with recent ACS receiving high-intensity statins had the highest achievement of

both lipid goals: LDL-C <1.8 mmol/L was 53% and non-HDL-C <2.6 mmol/L was 65%.

LDL-C and non-HDL-C goal achievement by LMT regimen was somewhat difficult to

interpret due to the unadjusted nature of analyses and potential self-selection bias,

resulting from the choice of LMT regimen in clinical practice being influenced by

baseline lipid levels and other patient-level factors.


Mean LDL-C was 2.4 mmol/L with approximately 26% achieving LDL-C <1.8 mmol/L.

Mean non-HDL-C was 3.2 mmol/L with approximately 33% achieving non-HDL-C <2.6

mmol/L. A summary of mean LDL-C and non-HDL-C levels and lipid goal achievement

are presented in Supplemental table S7. Achievement of LDL-C and non-HDL-C goals

was highest for the T1DM with CKD subgroup and lowest for the CKD alone subgroup.

The T1DM with CKD subgroup receiving medium-intensity statins had the highest lipid

goal achievement: 52% for LDL-C <1.8 mmol/L and 69% for non-HDL-C <2.6 mmol/L.

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Discussion

The use of statins for reducing atherogenic lipid levels is recommended across all global

guidelines for the prevention of incident ASCVD events. Recent guidelines have shifted

towards an approach of consistent and immediate initiation of the appropriate statin

intensity regimen for a particular indication regardless of baseline lipid levels. In

contrast, the standard approach has been to lower LDL-C (or non-HDL-C) below

defined thresholds. Our study, representing a UK general-practice population at high

risk for ASCVD events, provides several insights regarding the state of compliance with

the updated NICE 2014 guidelines,7 which focus on the intensity of the statin regimen.

As a comparison, we also report on compliance with the ESC/EAS 2011 guidelines,8

which focus on treatment to defined LDL-C goals.

We observed that 79% of individuals with ASCVD were receiving statin treatment,

but that only 6% were prescribed a regimen compliant with the updated NICE guidelines

(atorvastatin 80 mg or equivalent). For the non-ASCVD group, we observed that 62%

were receiving statin treatment, but that only 15% were prescribed a regimen compliant

with the guidelines (at least atorvastatin 20 mg or equivalent). Extrapolation of these

findings to the UK population indicated that, out of 3.3 million individuals with ASCVD,

2.4 million would require up-titration of statin therapy and 680 000 would require statin

initiation (31% de-novo initiation, 60% re-initiation, and 9% potential add-on to non-

statin LMT) to have full population-level compliance with these recommendations. Of

the 3.5 million individuals with high-risk non-ASCVD (i.e. fulfilling DM- and/or CKD-

based guideline criteria), 1.6 million would require up-titration of statin therapy and 1.4

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million would require statin initiation (59% de-novo initiation, 36% re-initiation, and 5%

potential add-on to non-statin LMT).

Our findings highlight the considerable gap between clinical practice in the UK and

the recommendations of the NICE 2014 guidelines. Assuming that implementation of

the guidelines represents best practice and would result in a reduction in ASCVD event

risk, the practical impact on patients, and in particular GPs, merits consideration. Firstly,

for patients who are well established on a treatment regimen, changes in therapy can

lead to reduced compliance, greater reporting of adverse events, and additional time

with the healthcare community to monitor the changes in therapy. Secondly, in an

environment where primary care is already stretched, the impact of counselling 90% of

eligible patients for statin regimen changes is likely to be considerable both on time and

resources available in primary care without, for instance, an increase in the number of

GPs. Finally, as cholesterol targets no longer appear in the updated 2014/15 Quality

Outcomes Framework (QOF) in UK for rewarding the provision of quality of care by

GPs,15 and with QOF lacking mention of statin intensity, it is unclear how narrowing of

the gap between guidelines and current practice might be effectively incentivised.

As mentioned earlier, an alternative approach to atherogenic lipid management is to

aim for lipid goal achievement as recommended in the ESC/EAS guidelines. For the

ASCVD population, we observed that achievement of LDL-C <1.8 mmol/L and non-

HDL-C <2.6 mmol/L8 was only 31% and 42% overall; 38% and 52% for those on

medium-intensity statins; and 37% and 48% for those on high-intensity statins.

Comparatively lower goal achievement for those on high-intensity statin likely reflected

the unadjusted nature of analysis, with patients on high-intensity statins being self-

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selected with a potentially higher baseline lipid level. For the non-ASCVD population

considered in the analysis (i.e. fulfilling DM- and/or CKD-based guideline criteria), the

ESC/EAS guidelines recommend the same thresholds of <1.8 mmol/L and <2.6 mmol/L

for LDL-C and non-HDL-C, respectively.8 We observed achievement of these goals in

only 26% and 33% of the non-ASCVD patients; 40% and 49% for those on medium-

intensity statin; and 36% and 42% for those on high-intensity statin.

For those not on any statin, treatment with a medium-intensity statin is expected to

lower LDL-C by 35%, while for those on medium-intensity statin, increasing the dose to

high-intensity is expected to lower LDL-C by an incremental 15%.7 Given that average

LDL-C levels for those not on a statin in both ASCVD and non-ASCVD cohorts was

approximately 3.0 mmol/L, and for those on medium-intensity statins in both ASCVD

and non-ASCVD cohorts was approximately 2.0 mmol/L, it is unlikely that average LDL-

C of <1.8 mmol/L can be achieved in these populations even with maximal statin

treatment. From the perspective of a treat to LDL-C goal approach, our results suggest

an expanded role for evidence-based add-on therapies for LDL-C lowering, which would

be ezetimibe based on available data from the IMPROVE-IT trial in 2014.16

Prior reports from a generalisable UK population describing LMT utilisation and lipid

attainment in ASCVD and non-ASCVD cohorts are limited. Our study provides novel

data on how these populations are treated and how effective the treatment has been.

The recent EUROASPIRE IV study, representing the 2012-2013 time period, was

conducted in patients with a history of hospitalisation due to a coronary event with an

assessment date of 6 months to 3 years post event.17 The study reported LDL-C <1.8

mmol/L achievement as only 19%. To our knowledge, the most recent study that

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reported statin use in a generalisable UK population at high CV risk found statin use in

2007 as 72% for patients with a history of MI or coronary revascularisation and 36%

those with a history of angina but not MI.18 Statin use in the UK in those with ASCVD

without coronary conditions (e.g. ischaemic stroke or PAD) appears to be even further

under-reported. From 1995-2005, in individuals aged ≥50 years with a history of stroke

(not limited to ischaemic stroke), 32% of men and 26% of women were receiving

treatment with LMT.19 Data on statin use in individuals with DM or CKD without ASCVD

also do not appear to be well reported. During 2006-2008, a diabetes registry

representing GPs in Scotland found 68% individuals with DM without ASCVD were

prescribed a statin.20 When compared to these data, our study suggests statin use has

increased in the UK. This increase is likely due to a multitude of influences, including

the NICE 2008 guidelines,21 landmark trials such as SPARCL which demonstrated the

benefits of statins in the post-ischaemic stroke population,22 and incorporation of statins

and lipid monitoring as quality measures in major pay-for-performance initiatives in the

UK.23

The continued recommendation for statin therapy for the ASCVD population from

both the 2008 to the 2014 NICE guidelines 7,21 suggest that the 21% rate of statin non-

use in this population is largely due to discontinuation, a hypothesis that is supported by

our findings which indicate that approximately 60% of statin non-use in the ASCVD

population can be attributed to discontinuation (hence overall 13% [=21%*60%] of statin

non-use in ASCVD population can be attributed to discontinuation in our study). High

rates of statin discontinuation have been documented in the literature. For example, in a

UK primary-care database analysis representing the 1997-2006 time period, 20% of

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patients initiated on a statin after an MI discontinued therapy at 1 year.24 For the non-

ASCVD population, the higher observed rate of statin non-use (38%) likely reflects not

only statin discontinuation but many patients who have never been prescribed LMT. Our

study suggests that approximately 59% of statin non-use in the non-ASCVD population

can be attributed to non-initiation of LMT therapy. Prior to the 2014 NICE guidelines,

some of these patients may not have qualified for LMT due to higher risk thresholds in

the NICE 2008 guidelines and the absence of certain conditions such as CKD as a

stand-alone criterion for statin therapy.7,21

Limitations

Availability of demographic and clinical characteristics was limited to information

available in the GP database. Certain data such as body-mass index, ethnicity, blood

pressure, and smoking status were not available for all patients. Lipid measurements

were not prospectively specified and the study cohort represents individuals with an

available lipid profile measurement, introducing the possibility of bias in findings. The

definition of LMT utilisation at the time of lipid measurements was optimised to provide

valid “on-treatment” measures, but ensuring whether patients fully took their prescribed

medications was not feasible from the database. For consistency we based LMT

categorization on statins regardless of concomitant non-statin medications. This meant,

for example, atorvastatin 10 mg + ezetimibe was categorized under medium potency

statin, even though its overall lipid-lowering efficacy may be close to atorvastatin 80 mg.

However, this is unlikely to have significant impact on findings as the proportion of these

instances was relatively low.

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Conclusions

In the UK, although 79% and 62% of ASCVD and high-risk non-ASCVD patients

respectively, received treatment with statin therapy, there exists a large gap relative to

the NICE 2014 guidelines recommendations, with approximately 90% of both

populations requiring modification to their existing therapy. Extrapolating these results to

the UK population, approximately 3 million ASCVD and 3 million high-risk non-ASCVD

individuals (i.e. fulfilling DM- and/or CKD-based guideline criteria) would require either

statin up-titration or initiation in order to attain compliance with NICE 2014 guidelines.

Achievement of ESC/EAS 2011 guideline criteria was also suboptimal, as approximately

two-thirds of individuals receiving moderate- or high-intensity statins were not at

recommended LDL-C goal.

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Contributors

Dylan Steen was involved with the design of the study, interpretation of data, and critical

review of drafts.

Irfan Khan was involved with the design of the study, interpretation of data, and critical

review of drafts.

David Ansell was involved with the design of the study, acquisition, analysis, and

interpretation of data, and critical review of drafts.

Robert J. Sanchez was involved with the design of the study, interpretation of data, and

critical review of drafts.

Kausik K. Ray was involved with the design of the study, interpretation of data, and


All authors provided final approval of the submitted manuscript.

Medical writing support was provided by Jeff Alexander from SNELL Medical

Communication, supported by Sanofi and Regeneron. Editorial assistance for later

drafts was provided by Neil Venn from Prime Medica, supported by Sanofi and

Regeneron.

Funding

This study was funded by Sanofi and Regeneron.

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Competing interests

Dylan Steen receives modest consulting fees from Sanofi and Regeneron. Irfan Khan is

a stockholder and employee of Sanofi. David Ansell is an employee of IMS Health.

Robert Sanchez is a stockholder and employee of Regeneron Pharmaceuticals, Inc.

Kausik Ray has received honoraria for advisory boards, lectures, or for serving on the

steering committee for clinical trials from Amgen, Sanofi, Regeneron, Pfizer,

AstraZeneca, Aegerion, Kowa, ISIS Pharma, MedCo, Cerenis, and Resverlogix, and

has received research support by grants to his institution from Pfizer, MSD, Amgen,

Sanofi, and Regeneron.

Ethics approval

This study was approved by the Scientific Review Committee, an independent UK-

based ethics committee established to review studies from The Health Improvement

Network (THIN).

Data sharing statement

The original analytic dataset is available on request by emailing the corresponding

author: [email protected].

Transparency

Dr Steen, as the lead author (the manuscript's guarantor) affirms that the manuscript is

an honest, accurate, and transparent account of the study being reported; no important

aspects of the study have been omitted and any discrepancies from the study as

planned have been explained.

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Copyright Statement

The Corresponding Author has the right to grant on behalf of all authors and does grant

on behalf of all authors, a worldwide licence to the Publishers and its licensees in

perpetuity, in all forms, formats and media (whether known now or created in the

future), to i) publish, reproduce, distribute, display and store the Contribution, ii)

translate the Contribution into other languages, create adaptations, reprints, include

within collections and create summaries, extracts and/or, abstracts of the Contribution,

iii) create any other derivative work(s) based on the Contribution, iv) to exploit all

subsidiary rights in the Contribution, v) the inclusion of electronic links from the

Contribution to third party material where-ever it may be located; and, vi) licence any

third party to do any or all of the above.

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References

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atorvastatin after stroke or transient ischemic attack. N Engl J Med.

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Fig 1. Determination of treatment status as of the index date

Blue bars representing scenarios A and B (medication supply via recorded prescription [Rx] on or within 30 days prior

to the index date) define the patient as being treated as of the index date. The red bar representing scenario C

(medication supply via recorded Rx more than 30 days prior to the index date) defines the patient as not being

treated as of the index date.

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Fig 2: Flowchart of the cohort selection for the study

*ASCVD includes acute coronary syndrome, other coronary heart disease, ischaemic stroke/transient ischaemic

attack, and peripheral arterial disease.

†Includes type 2 diabetes mellitus with QRISK2 ≥10%, type 1 diabetes mellitus with age >40 years, and chronic

kidney disease not meeting the previous diabetes mellitus criteria.

ASCVD=atherosclerotic cardiovascular disease; THIN=The Health Improvement Network

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Table 1. Baseline characteristics for the overall ASCVD and non-ASCVD cohorts and subgroups

ASCVD cohort (n=91 497) Non-ASCVD cohort (n=92 086)

Recent ACS (n=3112, 3%)

Other CHD (n=58 348,

64%)

Ischaemic stroke / TIA (n=19 785,

22%)

PAD (n=10 234,

11%) Total ASCVD

(n=91 497)

T2DM with CKD

(n=11 102, 12%)

T2DM without CKD

(n=52 556, 57%)

T1DM with CKD

(n=749, 1%)

T1DM without CKD

(n=4204, 5%)

CKD alone (n=23 475,

25%)

Total non-ASCVD

(n=92 086)

Demographic characteristics

Age, mean, years (SD) 67.8 (12.8) 72.8 (10.5) 73.0 (11.8) 72.3 (10.6) 72.6 (10.9) 75.7 (9.2) 67.2 (10.3) 69.7 (12.0) 57.2 (11.1) 74.6 (10.6) 69.7 (11.3)

Male, % 66.5 63.5 50.3 62.8 60.7 41.3 58.6 40.7 57.6 35.0 50.3

Social deprivation index*, mean (SD)

2.7 (1.4) 2.7 (1.4) 2.6 (1.4) 2.8 (1.4) 2.7 (1.4) 2.7 (1.4) 2.8 (1.4) 2.7 (1.5) 2.6 (1.4) 2.6 (1.4) 2.7 (1.4)

Ethnicity, %

White 28.3 30.3 29.1 30.0 30.0 29.0 29.4 25.1 30.0 27.9 28.9

South Asian 1.9 1.5 1.1 0.7 1.4 2.0 4.1 1.5 1.6 1.0 2.9

Black Caribbean / African 0.3 0.3 0.6 0.4 0.3 1.2 1.1 1.6 1.3 0.7 1.0

Chinese / other East Asian 13.2 12.6 12.9 12.3 12.6 13.8 12.9 13.4 13.7 14.5 13.4

Not recorded 56.4 55.4 56.4 56.6 55.8 54.0 52.5 58.5 53.3 55.9 53.7

Current smoker, % 15.2 12.1 13.5 26.6 14.1 7.0 14.9 10.8 16.3 7.1 11.9

BMI, mean, kg/m2 (SD) 28.4 (5.4) 28.6 (5.3) 27.8 (5.5) 27.6 (5.4) 28.3 (5.4) 30.4 (6.2) 30.9 (6.3) 29.8 (6.3) 28.3 (5.8) 28.3 (5.5) 30.1 (6.2)

Systolic BP, mean (SD) 128.9 (17.8) 131.5 (15.7) 133.1 (15.8) 134.6 (16.3) 132.1 (15.9) 134.5 (15.0) 134.7 (14.1) 134.7 (16.2) 131.1 (14.8) 134.1 (15.8) 134.3 (14.8)

Baseline clinical characteristics

Recent ACS, % 100.0 0.0 0.0 0.0 3.4 N/A N/A N/A N/A N/A N/A

Other CHD, % 64.2 100.0 0.0 0.0 66.0 N/A N/A N/A N/A N/A N/A

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Ischaemic stroke/TIA, % 7.6 10.5 100.0 0.0 28.6 N/A N/A N/A N/A N/A N/A

PAD, % 10.1 11.2 14.0 100.0 21.7 N/A N/A N/A N/A N/A N/A

DM, % 27.0 30.1 25.6 33.7 29.4 100.0 100.0 100.0 100.0 7.1 76.3

Hypertension, % 50.4 61.5 62.1 64.2 61.5 77.4 62.2 74.4 41.8 73.2 66.0

History of CHF, % 14.0 11.2 4.2 5.1 9.1 1.4 0.5 6.9 1.0 7.1 2.4

CKD, stage III, % 17.2 24.4 22.1 23.0 23.5 100.0 0.0 100.0 0.0 100.0 38.2

CKD, stage IV-V, %‡ 0.2 0.3 0.2 0.3 0.2 1.2 0.0 2.0 0.0 0.8 0.3

Concomitant medication use¶

Beta-blockers, % 81.4 60.1 23.5 22.4 48.7 N/A N/A N/A N/A N/A N/A

ACEI/ARBs, % 85 65.3 52.1 52.4 61.7 74.6 59.3 77.8 52.7 59.9 61.1

Antiplatelets,# % 52.5 13.5 29.7 15.4 18.5 N/A N/A N/A N/A N/A N/A

*Social deprivation index is defined by Townsend deprivation index score analysed in quintiles, 1 = most affluent and 5 = least affluent.

†Includes Indian, Pakistani, Bangladeshi, and other South Asian individuals

‡Stage V CKD includes end-stage renal disease and dialysis.

¶Medication use on index date.

#Clopidogrel/ticagrelor/prasugrel

ASCVD subgroups represent hierarchical categorisation. Non-ASCVD categorisations have been simplified by consideration of the qualifiers QRISK2 ≥10% and age >40 years as implicit in the definitions of T2DM and

T1DM, respectively, with and without CKD, and of the qualifiers without T2DM+QRISK2 ≥10% or T1DM+ age >40 as implicit in the definition of CKD alone.

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ACEI=angiotensin converting enzyme inhibitor; ACS=acute coronary syndrome; ARB=angiotensin II receptor blocker; ASCVD=atherosclerotic cardiovascular disease; BMI=body-mass index; BP=blood pressure;

CHD=coronary heart disease; CHF=congestive heart failure; CKD=chronic kidney disease; DM=diabetes mellitus; N/A=not applicable; PAD=peripheral arterial disease; SD=standard deviation; T1DM=type 1 diabetes

mellitus; T2DM=type 2 diabetes mellitus; TIA=transient ischaemic attack.

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Table 2. Use of LMT in the overall ASCVD and non-ASCVD cohorts and subgroups


Recent ACS

(n=3112) Other CHD (n=58 348)

Ischaemic stroke / TIA (n=19 785)

PAD (n=10 234)

Total ASCVD (n=91 497)

T2DM with CKD

(n=11 102)

T2DM without CKD

(n=52 556)

T1DM with CKD

(n=749)

T1DM without CKD

(n=4204) CKD alone (n=23 475)

Total non-ASCVD

(n=92 086)

High-intensity statin, % 62.4 34.6 21.5 23.2 31.4 20.0 18.6 29.0 21.1 11.1% 17.0

Monotherapy, % 93.3 91.8 93.2 92.3 92.2 91.1 93.5 92.6 90.2 93.3 93.0

Plus ezetimibe, % 1.0 4.8 2.9 3.4 4.1 3.2 2.4 4.1 5.1 2.7 2.8

Plus other non-statin LMT, %

5.8 3.4 3.9 4.3 3.7 5.7 4.0 3.2 4.7 4.0 4.3

Medium-intensity statin, % 22.6 41.4 46.2 44.3 42.1 44.7 43.0 39.5 36.5 33.1 40.4

Monotherapy, % 98.6 97.9 98.7 98.6 98.2 97.9 98.4 96.3 97.7 98.9 98.4

Plus ezetimibe, % 0.6 1.2 0.7 0.6 1.0 0.6 0.6 1.7 1.4 0.5 0.6


0.9 0.9 0.5 0.8 0.8 1.5 1.0 2.0 1.0 0.7 1.0

Low-intensity statin, % 2.1 5.9 5.5 5.1 5.6 6.4 4.9 4.9 4.4 4.8 5.0

Monotherapy, % 93.8 95.9 97.4 97.1 96.3 96.2 98.1 89.2 95.6 98.3 97.7

Plus ezetimibe, % 6.3 3.2 1.7 2.3 2.8 2.3 1.1 8.1 2.7 1.0 1.4


0.0 0.9 0.8 0.6 0.8 1.6 0.7 2.7 1.6 0.7 0.9

Non-statins only, % 0.9 2.0 1.7 1.9 1.9 2.5 1.6 3.9 2.0 1.7 1.8

Ezetimibe, % 70.4 61.3 65.5 55.6 61.6 47.9 54.2 58.6 61.6 45.5 51.5

Other non-statin LMT, % 29.6 38.7 34.5 44.4 38.4 52.1 45.8 41.4 38.4 54.5 48.5

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Not currently treated by LMT, %

12.1 16.2 25.1 25.4 19.0 26.4 31.9 22.7 35.9 49.4 35.8

Previously on high-intensity statin, %

20.7 16.4 8.6 9.3 13.2 7.7 6.1 18.2 9.1 3.3 5.5

Previously on medium-intensity statin, %

22.8 40.9 37.9 33.0 38.4 33.2 27.5 30.6 29.9 17.7 24.7

Previously on low-intensity statin, %

5.6 10.0 6.9 6.8 8.5 7.3 4.9 10.0 4.4 3.9 4.7

Previously on non-statin LMT, %

4.8 7.2 4.8 3.6 5.9 6.1 3.5 5.3 3.8 2.4 3.4

No previous LMT, % 46.1 25.5 41.8 47.3 34.0 45.7 58.0 35.9 52.8 72.7 61.7

Numbers in the grey bars denote absolute percentages, and add up to 100% vertically. Numbers in the white bars are relative percentages of the absolute percentages in the grey bars. ASCVD subgroups represent

hierarchical categorisation. Non-ASCVD categorisations have been simplified by consideration of the qualifiers QRISK2 ≥10% and age >40 years as implicit in the definitions of T2DM and T1DM, respectively, with and

without CKD, and of the qualifiers without T2DM+QRISK2 ≥10% or T1DM+ age >40 as implicit in the definition of CKD alone.

ACS=acute coronary syndrome; ASCVD=atherosclerotic cardiovascular disease; CHD=coronary heart disease; CKD=chronic kidney disease; LMT=lipid modifying therapy; PAD=peripheral arterial disease; T1DM=type

1 diabetes mellitus; T2DM=type 2 diabetes mellitus; TIA=transient ischaemic attack

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Table 3. Statin treatment according to NICE guidelines in the overall ASCVD and non-ASCVD cohorts and subgroups


Recent ACS (n=3112)

Other CHD (n=58 348)


PAD (n=10 234)


T2DM with CKD

(n=11 102)

T2DM without CKD

(n=52 556)

T1DM with CKD

(n=749)

T1DM without CKD

(n=4204)

CKD alone (n=23 475)

Total non-ASCVD

(n=92 086)

Study cohort, % (N)

Treated with statins according to NICE guidelines*

33.1 (1029)

6.7 (3934)

2.0 (400)

2.2 (221)

6.1 (5584)

18.6 (2065)

17.2 (9038)

26.2 (196)

19.3 (812)

10.3 (2421)

15.8 (14 532)

Treated with statins but not according to NICE guidelines

54.0 (1679)

75.1 (43 802)

71.2 (14 079)

70.5 (7216)

73.0 (66 776)

52.5 (5825)

49.3 (25 913)

47.3 (354)

42.7 (1796)

38.6 (9062)

46.6 (42 950)

Treated with only non-statin LMT 0.9 (27)

2.0 (1188)

1.7 (339)

1.9 (196)

1.9 (1750)

2.5 (282)

1.6 (858)

3.9 (29)

2.0 (86)

1.7 (402)

1.8 (1657)

Not treated by LMT 12.1 (377)

16.2 (9424)

25.1 (4967)

25.4 (2601)

19.0 (17 369)

26.4 (2930)

31.9 (16 747)

22.7 (170)

35.9 (1510)

49.4 (11 590)

35.8 (32 947)

Adjusted extrapolation to the UK population, N

Treated with statins according to NICE guidelines*

34 085 147 215 15 653 4869 201 822 112 119 209 589 10 642 18 830 156 621 507 801

Treated with statins but not according to NICE guidelines

55 615 1 639 122 550 930 158 966 2 404 633 316 269 600 916 19 220 41 649 586 243 1 564 297

Treated with only non-statin LMT

894 44 456 13 266 4318 62 934 15 311 19 897 1575 1994 26 006 64 783

Not treated by LMT

12 488 352 657 194 365 57 299 616 809 159 085 388 359 9230 35 017 749 786 1 341 477

*NICE guidelines recommendations for ASCVD: at least atorvastatin 80 mg or equivalent (i.e. atorvastatin 80 mg, rosuvastatin 40 mg). NICE guidelines recommendations for non-ASCVD high risk: at least atorvastatin

20 mg or equivalent (i.e. atorvastatin 20, 40 and 80 mg, rosuvastatin 10, 20 and 40 mg, and simvastatin 80 mg).



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ACS=acute coronary syndrome; ASCVD=atherosclerotic cardiovascular disease; CHD=coronary heart disease; CKD=chronic kidney disease; LMT=lipid modifying therapy; NICE=National Institute for Health and Care

Excellence; PAD=peripheral arterial disease; T1DM=type 1 diabetes mellitus; T2DM=type 2 diabetes mellitus; TIA=transient ischaemic attack; UK=United Kingdom

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Supplementary Appendix

Methodology for adjusted extrapolation to the United Kingdom (UK) population

Findings on the number of patients treated according to National Institute for Health and

Care Excellence (NICE) 2014 guidelines were extrapolated to the UK population via the

following methodology that accounted for adjustments by patient demographic and

clinical profiles. The study cohort was initially divided into mutually exclusive strata

based on status representing presence of coronary heart disease (CHD; including

recent acute coronary syndrome [ACS] and other CHD), ischaemic stroke / transient

ischaemic attack (TIA), peripheral arterial disease (PAD), diabetes mellitus (DM),

chronic kidney disease (CKD), dichotomous age groups (20–70 years versus ≥70

years), and gender. An example of strata would be a profile representing male, aged

≥70 years, with CHD and DM. Differential weights by these mutually exclusive strata

were then estimated via an optimisation algorithm to minimise the difference between

estimated totals for aggregate categories (not mutually exclusive) representing CHD,

ischaemic stroke/TIA, PAD, DM, CKD, age groups, and gender, and their reported

prevalence in the UK based on published sources. The estimated weights by strata

were then utilised to scale the results. The methodology helped ensure the extrapolation

accounted for differential scaling by patient profiles and eliminated double counting due

to overlap between conditions. Estimation of weights via optimisation methodology was

conducted using Excel Solver.

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SUPPLEMENTAL TABLE S1. Standardised Diagnostic Read Codes Used to Define

Patient Cohorts

ASCVD

ACS

G30..00 ACUTE MYOCARDIAL INFARCTION

G30..11 ATTACK - HEART

G30..12 Coronary thrombosis

G30..13 CARDIAC RUPTURE FOLLOWING MYOCARDIAL INFARCTION (MI)

G30..14 HEART ATTACK

G30..15 MI - ACUTE MYOCARDIAL INFARCTION

G30..16 Thrombosis - coronary

G300.00 ACUTE ANTEROLATERAL INFARCTION

G301.00 OTHER SPECIFIED ANTERIOR MYOCARDIAL INFARCTION

G301000 ACUTE ANTEROAPICAL INFARCTION

G301100 ACUTE ANTEROSEPTAL INFARCTION

G301z00 ANTERIOR MYOCARDIAL INFARCTION NOS

G302.00 ACUTE INFEROLATERAL INFARCTION

G303.00 ACUTE INFEROPOSTERIOR INFARCTION

G304.00 POSTERIOR MYOCARDIAL INFARCTION NOS

G305.00 LATERAL MYOCARDIAL INFARCTION NOS

G306.00 TRUE POSTERIOR MYOCARDIAL INFARCTION

G307.00 ACUTE SUBENDOCARDIAL INFARCTION

G307000 ACUTE NON-Q WAVE INFARCTION

G307100 ACUTE NON-ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

G308.00 INFERIOR MYOCARDIAL INFARCTION NOS

G309.00 ACUTE Q-WAVE INFARCT

G30B.00 ACUTE POSTEROLATERAL MYOCARDIAL INFARCTION

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G30X.00 ACUTE TRANSMURAL MYOCARDIAL INFARCTION OF UNSPECIFIED SITE

G30X000 ACUTE ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

G30y.00 OTHER ACUTE MYOCARDIAL INFARCTION

G30y000 ACUTE ATRIAL INFARCTION

G30y100 ACUTE PAPILLARY MUSCLE INFARCTION

G30y200 ACUTE SEPTAL INFARCTION

G30yz00 OTHER ACUTE MYOCARDIAL INFARCTION NOS

G30z.00 ACUTE MYOCARDIAL INFARCTION NOS

G31..00 Other acute and subacute ischaemic heart disease

G310.00 Postmyocardial infarction syndrome

G310.11 Dressler’s syndrome

G311500 Acute coronary syndrome

G312.00 Coronary thrombosis not resulting in myocardial infarction

G31y.00 Other acute and subacute ischaemic heart disease

G31y000 Acute coronary insufficiency

G31y100 MICROINFARCTION OF HEART

G31y200 Subendocardial ischaemia

G31y300 Transient myocardial ischaemia

G31yz00 Other acute and subacute ischaemic heart disease NOS

G35..00 Subsequent myocardial infarction

G350.00 Subsequent myocardial infarction of anterior wall

G351.00 Subsequent myocardial infarction of inferior wall

G353.00 Subsequent myocardial infarction of other sites

G35X.00 Subsequent myocardial infarction of unspecified site

G36..00 Certain current complication follow acute myocardial infarct

G360.00 Haemopericardium/current comp following acute myocardial infarction

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G361.00 Atrial septal defect/current comp following acute myocardial infarction

G362.00 Ventric septal defect/current comp following acute myocardial infarction

G363.00 Rupture of cardiac wall without haemopericard/current comp following acute myocardial infarction

G364.00 Ruptur chordae tendinae/current comp following acute myocardial infarction

G365.00 Rupture papillary muscle/current comp following acute myocardial infarction

G366.00 Thrombosis atrium,auric appendvent/current comp following acute myocardial infarction

G38..00 Postoperative myocardial infarction

G380.00 Postoperative transmural myocardial infarction anterior wall

G381.00 Postoperative transmural myocardial infarction inferior wall

G382.00 Postoperative transmural myocardial infarction other sites

G383.00 Postoperative transmural myocardial infarction unspecified site

G384.00 Postoperative subendocardial myocardial infarction

G38z.00 Postoperative myocardial infarction, unspecified

Gyu3400 [X]ACUTE TRANSMURAL MYOCARDIAL INFARCTION OF UNSPECIFIED SITE

Gyu3500 [X]Subsequent myocardial infarction of other sites

Gyu3600 [X]Subsequent myocardial infarction of unspecified site

G311.00 Preinfarction syndrome

G311.11 Crescendo angina

G311.12 Impending infarction

G311.13 Unstable angina

G311.14 Angina at rest

G311000 Myocardial infarction aborted

G311011 MI - myocardial infarction aborted

G311100 Unstable angina

G311200 Angina at rest

G311300 Refractory angina

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G311400 Worsening angina

G311z00 Preinfarction syndrome NOS

G330.00 Angina decubitus

G330000 Nocturnal angina

G330z00 Angina decubitus NOS

G33z500 Post infarct angina

G33z600 New onset angina

Other CHD

792E000 Emergency percutaneous coronary intervention

7920.00 SAPHENOUS VEIN GRAFT REPLACEMENT OF CORONARY ARTERY

7920.11 SAPHENOUS VEIN GRAFT BYPASS OF CORONARY ARTERY

7921.00 OTHER AUTOGRAFT REPLACEMENT OF CORONARY ARTERY

7921.11 OTHER AUTOGRAFT BYPASS OF CORONARY ARTERY

7922.00 ALLOGRAFT REPLACEMENT OF CORONARY ARTERY

7922.11 ALLOGRAFT BYPASS OF CORONARY ARTERY

7923.00 PROSTHETIC REPLACEMENT OF CORONARY ARTERY

7923.11 PROSTHETIC BYPASS OF CORONARY ARTERY

7924.00 REVISION OF BYPASS FOR CORONARY ARTERY

7925.00 CONNECTION OF MAMMARY ARTERY TO CORONARY ARTERY

7925.11 CREATION OF BYPASS FROM MAMMARY ARTERY TO CORONARY ARTERY

7926.00 CONNECTION OF OTHER THORACIC ARTERY TO CORONARY ARTERY

7927.00 OTHER OPEN OPERATIONS ON CORONARY ARTERY

7928.00 TRANSLUMINAL BALLOON ANGIOPLASTY OF CORONARY ARTERY

7928.11 PERCUTANEOUS BALLOON CORONARY ANGIOPLASTY

7929.00 OTHER THERAPEUTIC TRANSLUMINAL OPERATIONS ON CORONARY ARTERY

7920000 SAPHENOUS VEIN GRAFT REPLACEMENT OF ONE CORONARY ARTERY

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7920100 SAPHENOUS VEIN GRAFT REPLACEMENT OF TWO CORONARY ARTERIES

7920200 SAPHENOUS VEIN GRAFT REPLACEMENT OF THREE CORONARY ARTERIES

7920300 SAPHENOUS VEIN GRAFT REPLACEMENT OF FOUR+ CORONARY ARTERIES

7921000 AUTOGRAFT REPLACEMENT OF ONE CORONARY ARTERY NEC

7921100 AUTOGRAFT REPLACEMENT OF TWO CORONARY ARTERIES NEC

7921200 AUTOGRAFT REPLACEMENT OF THREE CORONARY ARTERIES NEC

7921300 AUTOGRAFT REPLACEMENT OF FOUR OF MORE CORONARY ARTERIES NEC

7922000 ALLOGRAFT REPLACEMENT OF ONE CORONARY ARTERY

7922100 ALLOGRAFT REPLACEMENT OF TWO CORONARY ARTERIES

7922200 ALLOGRAFT REPLACEMENT OF THREE CORONARY ARTERIES

7922300 ALLOGRAFT REPLACEMENT OF FOUR+ CORONARY ARTERIES

7923000 PROSTHETIC REPLACEMENT OF ONE CORONARY ARTERY

7923100 PROSTHETIC REPLACEMENT OF TWO CORONARY ARTERIES

7923200 PROSTHETIC REPLACEMENT OF THREE CORONARY ARTERIES

7923300 PROSTHETIC REPLACEMENT OF FOUR+ CORONARY ARTERIES

7924000 REVISION OF BYPASS FOR ONE CORONARY ARTERY

7924100 REVISION OF BYPASS FOR TWO CORONARY ARTERIES

7924200 REVISION OF BYPASS FOR THREE CORONARY ARTERIES

7924300 REVISION OF BYPASS FOR FOUR+ CORONARY ARTERIES

7924400 REVISION OF CONNECTION OF THORACIC ARTERY TO CORONARY ARTERY

7924500 REVISION OF IMPLANTATION OF THORACIC ARTERY INTO HEART

7925000 DOUBLE ANASTOMOSIS OF MAMMARY ARTERIES TO CORONARY ARTERIES

7925011 LIMA sequential anastomosis

7925012 RIMA sequential anastomosis

7925100 DOUBLE IMPLANT OF MAMMARY ARTERIES INTO CORONARY ARTERIES

7925200 SINGLE ANAST MAMMARY ART TO LEFT ANT DESCEND CORONARY ART

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7925300 SINGLE ANASTOMOSIS OF MAMMARY ARTERY TO CORONARY ARTERY NEC

7925311 LIMA single anastomosis

7925312 RIMA single anastomosis

7925400 SINGLE IMPLANTATION OF MAMMARY ARTERY INTO CORONARY ARTERY

7926000 DOUBLE ANASTOM THORACIC ARTERIES TO CORONARY ARTERIES NEC

7926100 DOUBLE IMPLANT THORACIC ARTERIES INTO CORONARY ARTERIES NEC

7926200 SINGLE ANASTOMOSIS OF THORACIC ARTERY TO CORONARY ARTERY NEC

7926300 SINGLE IMPLANTATION THORACIC ARTERY INTO CORONARY ARTERY NEC

7927500 OPEN ANGIOPLASTY OF CORONARY ARTERY

7928000 PERCUT TRANSLUMINAL BALLOON ANGIOPLASTY ONE CORONARY ARTERY

7928100 PERCUT TRANSLUM BALLOON ANGIOPLASTY MULT CORONARY ARTERIES

7928200 PERCUT TRANSLUM BALLOON ANGIOPLASTY BYPASS GRAFT CORONARY A

7928300 PERCUT TRANSLUM CUTTING BALLOON ANGIOPLASTY CORONARY ARTERY

7929000 PERCUTANEOUS TRANSLUMINAL LASER CORONARY ANGIOPLASTY

7929100 Percut transluminal coronary thrombolysis with streptokinase

7929111 Percut translum coronary thrombolytic therapy - streptokinase

7929200 PERCUTAN. TRANSLUM. INJECT THERAP SUBST TO CORONARY ARTERY NEC

7929200 Percut translum inject therap subst to coronary artery NEC

7929300 ROTARY BLADE CORONARY ANGIOPLASTY

7929400 INSERTION OF CORONARY ARTERY STENT

7929500 INSERTION OF DRUG-ELUTING CORONARY ARTERY STENT

7929600 PERCUTANEOUS TRANSLUMINAL ATHERECTOMY OF CORONARY ARTERY

790H300 Revascularisation of wall of heart

792..00 CORONARY ARTERY OPERATIONS

792..11 CORONARY ARTERY BYPASS GRAFT OPERATIONS

7920y00 SAPHENOUS VEIN GRAFT REPLACEMENT OF CORONARY ARTERY OS

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7920z00 SAPHENOUS VEIN GRAFT REPLACEMENT CORONARY ARTERY NOS

7921y00 OTHER AUTOGRAFT REPLACEMENT OF CORONARY ARTERY OS

7921z00 OTHER AUTOGRAFT REPLACEMENT OF CORONARY ARTERY NOS

7922y00 OTHER SPECIFIED ALLOGRAFT REPLACEMENT OF CORONARY ARTERY

7922z00 ALLOGRAFT REPLACEMENT OF CORONARY ARTERY NOS

7923y00 OTHER SPECIFIED PROSTHETIC REPLACEMENT OF CORONARY ARTERY

7923z00 PROSTHETIC REPLACEMENT OF CORONARY ARTERY NOS

7924y00 OTHER SPECIFIED REVISION OF BYPASS FOR CORONARY ARTERY

7924z00 REVISION OF BYPASS FOR CORONARY ARTERY NOS

7925y00 CONNECTION OF MAMMARY ARTERY TO CORONARY ARTERY OS

7925z00 CONNECTION OF MAMMARY ARTERY TO CORONARY ARTERY NOS

7926y00 CONNECTION OF OTHER THORACIC ARTERY TO CORONARY ARTERY OS

7926z00 CONNECTION OF OTHER THORACIC ARTERY TO CORONARY ARTERY NOS

7927y00 OTHER SPECIFIED OTHER OPEN OPERATION ON CORONARY ARTERY

7927z00 OTHER OPEN OPERATION ON CORONARY ARTERY NOS

7928y00 TRANSLUMINAL BALLOON ANGIOPLASTY OF CORONARY ARTERY OS

7928z00 TRANSLUMINAL BALLOON ANGIOPLASTY OF CORONARY ARTERY NOS

7929y00 OTHER THERAPEUTIC TRANSLUMINAL OP ON CORONARY ARTERY OS

7929z00 OTHER THERAPEUTIC TRANSLUMINAL OP ON CORONARY ARTERY NOS

792A.00 DIAGNOSTIC TRANSLUMINAL OPERATIONS ON CORONARY ARTERY

792B.00 REPAIR OF CORONARY ARTERY NEC

792B000 Endarterectomy of coronary artery NEC

792By00 Other specified repair of coronary artery

792Bz00 Repair of coronary artery NOS

792C.00 OTHER REPLACEMENT OF CORONARY ARTERY

792C000 REPLACEMENT OF CORONARY ARTERIES USING MULTIPLE METHODS

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792Cy00 OTHER SPECIFIED REPLACEMENT OF CORONARY ARTERY

792Cz00 REPLACEMENT OF CORONARY ARTERY NOS

792D.00 OTHER BYPASS OF CORONARY ARTERY

792Dy00 OTHER SPECIFIED OTHER BYPASS OF CORONARY ARTERY

792Dz00 OTHER BYPASS OF CORONARY ARTERY NOS

792E.00 Percutaneous coronary intervention

792y.00 OTHER SPECIFIED OPERATIONS ON CORONARY ARTERY

792z.00 Coronary artery operations NOS

793G.00 Perc translumin balloon angioplasty stenting coronary artery

793G000 Perc translum balloon angioplasty insert 1-2 drug elut stents cor art

793G100 Perc translum balloon angioplasty ins 3 or more drug elut stents cor art

793G200 Perc translum balloon angioplasty insert 1-2 stents cor art

793G300 Percutaneous cor balloon angioplasty 3 more stents cor art NEC

793Gy00 OS perc translum balloon angioplasty stenting coronary art

793Gz00 Perc translum balloon angioplasty stenting coronary art NOS

793K.00 Transluminal operations internal mammary artery side branch

793K000 Transluminal occlusion left internal mammary artery side branch

793Ky00 OS transluminal operations internal mammary art side branch

793Kz00 Transluminal operations internal mammary art side branch NOS

SP00300 MECHANICAL COMPLICATION OF CORONARY BYPASS

ZV45700 [V]Presence of aortocoronary bypass graft

3232.00 ECG: old myocardial infarction

14A3.00 H/O: myocardial infarct <60

14A4.00 H/O: myocardial infarct >60

14AH.00 H/O: Myocardial infarction in last year

14AT.00 History of myocardial infarction

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G30..17 Silent myocardial infarction

G32..00 Old myocardial infarction

G32..11 Healed myocardial infarction

G32..12 Personal history of myocardial infarction

G344.00 Silent myocardial ischaemia

8B3k.00 Coronary heart disease medication review

8CMP.00 Coronary heart disease care plan

8CR6.00 Coronary heart disease risk clinical management plan

8I37.00 Coronary heart disease monitoring refused

9Ob..00 Coronary heart disease monitoring administration

9Ob0.00 Attends coronary heart disease monitoring

9Ob1.00 Refuses coronary heart disease monitoring

9Ob2.00 Coronary heart disease monitoring default

9Ob3.00 Coronary heart disease monitoring 1st letter

9Ob4.00 Coronary heart disease monitoring 2nd letter

9Ob5.00 Coronary heart disease monitoring 3rd letter

9Ob6.00 Coronary heart disease monitoring verbal invitation

9Ob7.00 Coronary heart disease monitoring deleted

9Ob8.00 Coronary heart disease monitoring check done

9Ob9.00 Coronary heart disease monitoring telephone invite

G3...11 Arteriosclerotic heart disease

G3...12 Atherosclerotic heart disease

G34..00 Other chronic ischaemic heart disease

G340.00 Coronary atherosclerosis

G340.11 Triple vessel disease of the heart

G340.12 Coronary artery disease

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G340000 Single coronary vessel disease

G342.00 Atherosclerotic cardiovascular disease

G343.00 Ischaemic cardiomyopathy

G34y.00 Other specified chronic ischaemic heart disease

G34y000 Chronic coronary insufficiency

G34y100 Chronic myocardial ischaemia

G34yz00 Other specified chronic ischaemic heart disease NOS

G34z.00 Other chronic ischaemic heart disease NOS

G34z000 Asymptomatic coronary heart disease

G39..00 Coronary microvascular disease

3889.00 Euroscore for angina

14A5.00 H/O: angina pectoris

14AJ.00 H/O: angina in last year

187..00 Frequency of angina

388E.00 Canadian Cardiovascular Society classification of angina

388F.00 Cardiovascular Limitations and Symptoms Profile angina score

661M000 Angina self-management plan agreed

661N000 Angina self-management plan review

662K.00 Angina control

662K000 Angina control - good

662K100 Angina control - poor

662K200 Angina control - improving

662K300 Angina control - worsening

662Kz00 Angina control NOS

8B27.00 Antianginal therapy

8IEY.00 Referral to Angina Plan self-management programme declined

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8T04.00 Referral to Angina Plan self-management programme

G33..00 Angina pectoris

G331.11 Variant angina pectoris

G33z.00 Angina pectoris NOS

G33z000 Status anginosus

G33z100 Stenocardia

G33z200 Syncope anginosa

G33z300 Angina on effort

G33z400 Ischaemic chest pain

G33z700 Stable angina

G33zz00 Angina pectoris NOS

Gyu3000 [X]Other forms of angina pectoris

J421.11 Angina - abdominal

ZR37.00 Canadian Cardiovascular Society classification of angina

ZR3P.00 CLASP angina score


ZRB1.00 Euroscore for angina

Ischaemic stroke/TIA

G63..11 Infarction - precerebral

G632.00 Vertebral artery occlusion

G633.00 Multiple and bilateral precerebral arterial occlus

G63y000 Cerebral infarct due to thrombosis of precerebral arteries

G63y100 Cerebral infarction due to embolism of precerebral arteries

G64..00 Cerebral arterial occlusion

G64..11 CVA - cerebral artery occlusion

G64..12 Infarction - cerebral

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G64..13 Stroke due to cerebral arterial occlusion

G640.00 Cerebral thrombosis

G640000 Cerebral infarction due to thrombosis of cerebral

G64z.00 Cerebral infarction NOS

G64z.11 Brainstem infarction NOS

G64z.12 Cerebellar infarction

G64z000 Brainstem infarction

G64z100 Wallenberg syndrome

G64z200 Left sided cerebral infarction

G64z300 Right sided cerebral infarction

G64z400 Infarction of basal ganglia

G671000 Acute cerebrovascular insufficiency NOS

G677000 Occlusion and stenosis of middle cerebral artery

G677100 Occlusion and stenosis of anterior cerebral artery

G677200 Occlusion and stenosis of posterior cerebral arter

G677300 Occlusion and stenosis of cerebellar arteries

G677400 Occlusion and stenosis of multiple and bilat cerebral

G6W..00 Cereb infarct due unsp occlus/stenos precerebr art

G6W..00 Cereb infarct due unsp occlus/stenos precerebr arteries

G6X..00 Cereb infarct due/unspcf occlusn or sten/cerebr

G6X..00 Cereb infarct due/unspcf occlusn or sten/cerebrl artrs

Gyu6300 [X]Cereb infarct due/unspcf occlusn or sten/cerebrl artrs

Gyu6400 [X]Other cerebral infarction

Gyu6600 [X]Occlusion and stenosis of other cerebral arteries

Gyu6G00 [X]Cereb infarct due unsp occlus/stenos precerebr arteries

14AB.00 H/O: TIA

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1JK..00 Suspected transient ischaemic attack

8CRB.00 Transient ischaemic attack clinical management plan

8HBJ.00 Stroke / transient ischaemic attack referral

9Om..00 Stroke/transient ischaemic attack monitoring administration

9Om0.00 Stroke/transient ischaemic attack monitoring first letter

9Om1.00 Stroke/transient ischaemic attack monitoring second letter

9Om2.00 Stroke/transient ischaemic attack monitoring third letter

9Om3.00 Stroke/transient ischaemic attack monitoring verbal invitati

9Om4.00 Stroke/transient ischaemic attack monitoring telephone invte

F580200 Transient ischaemic deafness

ZV12D00 [V]Personal history of transient ischaemic attack

G65..00 Transient cerebral ischaemia

G65..11 Drop attack

G65..12 Transient ischaemic attack

G65..13 Vertebro-basilar insufficiency

G650.00 Basilar artery syndrome

G650.11 Insufficiency - basilar artery

G651.00 Vertebral artery syndrome

G651000 Vertebro-basilar artery syndrome

G652.00 Subclavian steal syndrome

G653.00 Carotid artery syndrome hemispheric

G654.00 Multiple and bilateral precerebral artery syndromes

G655.00 Transient global amnesia

G656.00 Vertebrobasilar insufficiency

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G657.00 Carotid territory transient ischaemic attack

G65y.00 Other transient cerebral ischaemia

G65z.00 Transient cerebral ischaemia NOS

G65z000 Impending cerebral ischaemia

G65z100 Intermittent cerebral ischaemia

G65zz00 Transient cerebral ischaemia NOS

14AB000 H/O amaurosis fugax

F423300 Retinal microembolism

F423400 Hollenhorst plaque

F423500 Retinal partial arterial occlusion NOS

F423600 Amaurosis fugax

F423700 Retinal transient arterial occlusion NOS

PAD

66f3.00 Aortic aneurysm monitoring

68B5100 Aortic aneurysm screening abnormal

7A11.00 Replacement of aneurysmal bifurcation of aorta

7A11000 Emerg repl aneurysm bifurc aorta by anast aorta to fem art

7A11100 Replace aneurysm bifurc aorta by anast aorta to femoral art

7A11200 Emerg repl aneurysm bifurc aorta by anast aorta to iliac a

7A11211 Y graft of abdominal aortic aneurysm (emergency)

7A11300 Replace aneurysm bifurc aorta by anast aorta to iliac artery

7A11311 Y graft abdominal aortic aneurysm

7A11y00 Replacement of aneurysmal bifurcation of aorta OS

7A11z00 Replacement of aneurysmal bifurcation of aorta NOS

7A13.11 Emergency repair of aortic aneurysm

7A13400 Emerg replace aneurysm abdom aorta by anast aorta/aorta NEC

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7A13411 Tube graft abdominal aortic aneurysm (emergency)

7A14.11 Aortic aneurysm repair

7A14400 Replace aneurysm abdominal aorta by anast aorta to aorta NEC

7A14411 Tube graft of abdominal aortic aneurysm

7A1B000 Endovascular stenting infrarenal abdominal aortic aneurysm

7A1B100 Endovascular stenting of suprarenal aortic aneurysm

7A1B600 Endovascular stenting for aortic aneurysm of bifurcation NEC

7A1B800 Endovascul insert stent infrarenal abdominal aortic aneurysm

7A1B900 Endovascular insertion stent for suprarenal aortic aneurysm

7A1BA00 Endovascular insertion of stent for thoracic aortic aneurysm

7A1BC00 Endovas insert stent for aortic aneurysm of bifurcation NEC

7A1C000 Endovas ins stent graft for infrarenal abdom aortic aneurysm

7A1C100 Endovas insert of stent graft for suprarenal aortic aneurysm

7A1C200 Endov insertion of stent graft for thoracic aortic aneurysm

G71..00 Aortic aneurysm

G713.00 Abdominal aortic aneurysm which has ruptured

G713.11 Ruptured abdominal aortic aneurysm

G713000 Ruptured suprarenal aortic aneurysm

G714.00 Abdominal aortic aneurysm without mention of rupture

G714.11 AAA - Abdominal aortic aneurysm without mention of rupture

G714000 Juxtarenal aortic aneurysm

G714200 Infrarenal abdominal aortic aneurysm

G714300 Aneurysm of suprarenal aorta

G715.00 Ruptured aortic aneurysm NOS

G715000 Thoracoabdominal aortic aneurysm, ruptured

G716.00 Aortic aneurysm without mention of rupture NOS

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G716000 Thoracoabdominal aortic aneurysm, without mention of rupture

G718.00 Leaking abdominal aortic aneurysm

G71z.00 Aortic aneurysm NOS

Gyu7100 [X]Aortic aneurysm of unspecified site, ruptured

Gyu7200 [X]Aortic aneurysm of unspecified site, nonruptured

7A20000 Replacement of carotid artery using graft

7A20100 Intracranial bypass to carotid artery

7A20200 Bypass to carotid artery NEC

7A20300 Endarterectomy and patch repair of carotid artery

7A20311 Carotid endarterectomy and patch

7A20400 Endarterectomy of carotid artery NEC

7A20500 High-flow inter extrac intrac byp ext carot art mid cer art

7A20600 Byp carot art anastom superfic tempor artery middle cere art

7A20700 Intracranial bypass from carotid artery NEC

7A20y00 Other specified reconstruction of carotid artery

7A20z00 Reconstruction of carotid artery NOS

7A21.00 Other open operations on carotid artery

7A21000 Repair of carotid artery NEC

7A21100 Ligation of carotid artery

7A22.00 Transluminal operations on carotid artery

7A22000 Percutaneous transluminal angioplasty of carotid artery

7A22200 Endovascular repair of carotid artery

7A22300 Percutaneous transluminal insertion stent carotid artery

7A22y00 Other specified transluminal operation on carotid artery

7A22z00 Transluminal operation on carotid artery NOS

G630.00 Basilar artery occlusion

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G631.00 Carotid artery occlusion

G631.11 Stenosis, carotid artery

G631.12 Thrombosis, carotid artery

G634.00 Carotid artery stenosis

G63y.00 Other precerebral artery occlusion

G63z.00 Precerebral artery occlusion NOS


G670.00 Cerebral atherosclerosis

G670.11 Precerebral atherosclerosis

G677.00 Occlusion/stenosis cerebral arts not result cerebral infarct

G70y000 Carotid artery atherosclerosis


G70y011 Carotid artery disease


Gyu6500 [X]Occlusion and stenosis of other precerebral arteries

SP01200 Mechanical complication of carotid artery bypass

14NB.00 H/O: Peripheral vascular disease procedure

662U.00 Peripheral vascular disease monitoring

9m1..00 Peripheral vascular disease monitoring invitation

9N4h.00 DNA - Did not attend peripheral vascular disease c

G63..00 Precerebral arterial occlusion

G63..12 Stenosis of precerebral arteries

G70..00 Atherosclerosis

G70..11 Arteriosclerosis

G700.00 Aortic atherosclerosis

G700.11 Aorto-iliac disease

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G702.00 Extremity artery atheroma

G702000 Monckeberg's medial sclerosis

G70z.00 Arteriosclerotic vascular disease NOS

G73..00 Other peripheral vascular disease

G73..11 Peripheral ischaemic vascular disease

G73..12 Ischaemia of legs

G73..13 Peripheral ischaemia

G733.00 Ischaemic foot

G734.00 Peripheral arterial disease

G73y.00 Other specified peripheral vascular disease

G73yz00 Other specified peripheral vascular disease NOS

G73z.00 Peripheral vascular disease NOS

G73z000 Intermittent claudication

G73z011 Claudication

G73z012 Vascular claudication

G73zz00 Peripheral vascular disease NOS

G784.00 Occlusion of artery of lower limb

G784000 Occlusion of dorsalis pedis artery

G784100 Occlusion of anterior tibial artery

G784200 Occlusion of posterior tibial artery

Gyu7400 [X]Other specified peripheral vascular diseases

Non-ASCVD

T2DM

66A3.00 Diabetic on diet only

66A4.00 Diabetic on oral treatment

66Ao.00 Diabetes type 2 review

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66At100 Type II diabetic dietary review

66At111 Type 2 diabetic dietary review

C100100 Diabetes mellitus, adult onset, no mention of comp

C100111 Maturity onset diabetes

C100112 Non-insulin dependent diabetes mellitus

C101100 Diabetes mellitus, adult onset, with ketoacidosis

C102.00 Diabetes mellitus with hyperosmolar coma

C102100 Diabetes mellitus, adult onset, with hyperosmolar

C103100 Diabetes mellitus, adult onset, with ketoacidotic

C105100 Diabetes mellitus, adult onset, + ophthalmic manif

C106100 Diabetes mellitus, adult onset, + neurological man

C107100 Diabetes mellitus, adult, + peripheral circulatory

C107200 Diabetes mellitus, adult with gangrene

C109.00 Non-insulin dependent diabetes mellitus

C109.11 NIDDM - Non-insulin dependent diabetes mellitus

C109.12 Type 2 diabetes mellitus

C109.13 Type II diabetes mellitus

C109200 Non-insulin-dependent diabetes mellitus with neuro

C109211 Type II diabetes mellitus with neurological compli

C109212 Type 2 diabetes mellitus with neurological complic

C109300 Non-insulin-dependent diabetes mellitus with multi

C109311 Type II diabetes mellitus with multiple complicati

C109312 Type 2 diabetes mellitus with multiple complicatio

C109400 Non-insulin dependent diabetes mellitus with ulcer

C109411 Type II diabetes mellitus with ulcer

C109412 Type 2 diabetes mellitus with ulcer

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C109500 Non-insulin dependent diabetes mellitus with gangr

C109511 Type II diabetes mellitus with gangrene

C109512 Type 2 diabetes mellitus with gangrene

C109700 Non-insulin dependent diabetes mellitus - poor con

C109711 Type II diabetes mellitus - poor control

C109712 Type 2 diabetes mellitus - poor control

C109900 Non-insulin-dependent diabetes mellitus without co

C109911 Type II diabetes mellitus without complication

C109912 Type 2 diabetes mellitus without complication

C109A00 Non-insulin dependent diabetes mellitus with monon

C109A11 Type II diabetes mellitus with mononeuropathy

C109A12 Type 2 diabetes mellitus with mononeuropathy

C109B00 Non-insulin dependent diabetes mellitus with polyn

C109B11 Type II diabetes mellitus with polyneuropathy

C109B12 Type 2 diabetes mellitus with polyneuropathy

C109D00 Non-insulin dependent diabetes mellitus with hypog

C109D11 Type II diabetes mellitus with hypoglycaemic coma

C109D12 Type 2 diabetes mellitus with hypoglycaemic coma

C109E00 Non-insulin depend diabetes mellitus with diabetic

C109E11 Type II diabetes mellitus with diabetic cataract

C109E12 Type 2 diabetes mellitus with diabetic cataract

C109F11 Type II diabetes mellitus with peripheral angiopat

C109F12 Type 2 diabetes mellitus with peripheral angiopath

C109G00 Non-insulin dependent diabetes mellitus with arthr

C109G11 Type II diabetes mellitus with arthropathy

C109G12 Type 2 diabetes mellitus with arthropathy

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C109H11 Type II diabetes mellitus with neuropathic arthrop

C109H12 Type 2 diabetes mellitus with neuropathic arthropa

C109J00 Insulin treated Type 2 diabetes mellitus

C109J11 Insulin treated non-insulin dependent diabetes mel

C109J12 Insulin treated Type II diabetes mellitus

C109K00 Hyperosmolar non-ketotic state in type 2 diabetes

C10C.00 Diabetes mellitus autosomal dominant

C10C.11 Maturity onset diabetes in youth

C10D.00 Diabetes mellitus autosomal dominant type 2

C10D.11 Maturity onset diabetes in youth type 2

C10F.00 Type 2 diabetes mellitus

C10F.11 Type II diabetes mellitus

C10F200 Type 2 diabetes mellitus with neurological complic

C10F211 Type II diabetes mellitus with neurological compli

C10F300 Type 2 diabetes mellitus with multiple complicatio

C10F311 Type II diabetes mellitus with multiple complicati

C10F400 Type 2 diabetes mellitus with ulcer

C10F411 Type II diabetes mellitus with ulcer

C10F500 Type 2 diabetes mellitus with gangrene

C10F511 Type II diabetes mellitus with gangrene

C10F700 Type 2 diabetes mellitus - poor control

C10F711 Type II diabetes mellitus - poor control

C10F900 Type 2 diabetes mellitus without complication

C10F911 Type II diabetes mellitus without complication

C10FA00 Type 2 diabetes mellitus with mononeuropathy

C10FA11 Type II diabetes mellitus with mononeuropathy

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C10FB00 Type 2 diabetes mellitus with polyneuropathy

C10FB11 Type II diabetes mellitus with polyneuropathy

C10FD00 Type 2 diabetes mellitus with hypoglycaemic coma

C10FD11 Type II diabetes mellitus with hypoglycaemic coma

C10FE00 Type 2 diabetes mellitus with diabetic cataract

C10FE11 Type II diabetes mellitus with diabetic cataract

C10FF00 Type 2 diabetes mellitus with peripheral angiopath

C10FF11 Type II diabetes mellitus with peripheral angiopat

C10FG00 Type 2 diabetes mellitus with arthropathy

C10FG11 Type II diabetes mellitus with arthropathy

C10FH00 Type 2 diabetes mellitus with neuropathic arthropa

C10FH11 Type II diabetes mellitus with neuropathic arthrop

C10FJ00 Insulin treated Type 2 diabetes mellitus

C10FJ11 Insulin treated Type II diabetes mellitus

C10FK00 Hyperosmolar non-ketotic state in type 2 diabetes

C10FK11 Hyperosmolar non-ketotic state in type II diabetes

C10FN00 Type 2 diabetes mellitus with ketoacidosis

C10FN11 Type II diabetes mellitus with ketoacidosis

C10FP00 Type 2 diabetes mellitus with ketoacidotic coma

C10FP11 Type II diabetes mellitus with ketoacidotic coma

C10FR00 Type 2 diabetes mellitus with gastroparesis

C10FR11 Type II diabetes mellitus with gastroparesis

C10FS00 Maternally inherited diabetes mellitus

C10N.00 Secondary diabetes mellitus

C10N000 Secondary diabetes mellitus without complication

C10y100 Diabetes mellitus, adult, + other specified manife

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C10z100 Diabetes mellitus, adult onset, + unspecified comp

L180600 Pre-existing diabetes mellitus, non-insulin-depend

C104100 Diabetes mellitus, adult onset, with renal manifes

C109000 Non-insulin-dependent diabetes mellitus with renal

C109011 Type II diabetes mellitus with renal complications

C109012 Type 2 diabetes mellitus with renal complications

C109C00 Non-insulin dependent diabetes mellitus with nephr

C109C11 Type II diabetes mellitus with nephropathy

C109C12 Type 2 diabetes mellitus with nephropathy

C10F000 Type 2 diabetes mellitus with renal complications

C10F011 Type II diabetes mellitus with renal complications

C10FC00 Type 2 diabetes mellitus with nephropathy

C10FC11 Type II diabetes mellitus with nephropathy

C10FL00 Type 2 diabetes mellitus with persistent proteinur

C10FL11 Type II diabetes mellitus with persistent proteinu

C10FM00 Type 2 diabetes mellitus with persistent microalbu

C10FM11 Type II diabetes mellitus with persistent microalb

C109100 Non-insulin-dependent diabetes mellitus with ophth

C109111 Type II diabetes mellitus with ophthalmic complica

C109112 Type 2 diabetes mellitus with ophthalmic complicat

C109600 Non-insulin-dependent diabetes mellitus with retin

C109611 Type II diabetes mellitus with retinopathy

C109612 Type 2 diabetes mellitus with retinopathy

C10F100 Type 2 diabetes mellitus with ophthalmic complicat

C10F111 Type II diabetes mellitus with ophthalmic complica

C10F600 Type 2 diabetes mellitus with retinopathy

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C10F611 Type II diabetes mellitus with retinopathy

C10FQ00 Type 2 diabetes mellitus with exudative maculopath

C10FQ11 Type II diabetes mellitus with exudative maculopat

T1DM

66An.00 Diabetes type 1 review

66At000 Type I diabetic dietary review


66AV.00 Diabetic on insulin and oral treatment

C100000 Diabetes mellitus, juvenile type, no mention of co

C100011 Insulin dependent diabetes mellitus

C101000 Diabetes mellitus, juvenile type, with ketoacidosi

C102000 Diabetes mellitus, juvenile type, with hyperosmola

C103000 Diabetes mellitus, juvenile type, with ketoacidoti

C105000 Diabetes mellitus, juvenile type, + ophthalmic man

C106000 Diabetes mellitus, juvenile, + neurological manife

C107000 Diabetes mellitus, juvenile +peripheral circulator

C108.00 Insulin dependent diabetes mellitus

C108.11 IDDM-Insulin dependent diabetes mellitus


C108.13 Type I diabetes mellitus

C108200 Insulin-dependent diabetes mellitus with neurologi

C108211 Type I diabetes mellitus with neurological complic


C108300 Insulin dependent diabetes mellitus with multiple

C108311 Type I diabetes mellitus with multiple complicatio


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C108400 Unstable insulin dependent diabetes mellitus

C108411 Unstable type I diabetes mellitus

C108412 Unstable type 1 diabetes mellitus

C108500 Insulin dependent diabetes mellitus with ulcer

C108511 Type I diabetes mellitus with ulcer


C108600 Insulin dependent diabetes mellitus with gangrene

C108611 Type I diabetes mellitus with gangrene


C108800 Insulin dependent diabetes mellitus - poor control

C108811 Type I diabetes mellitus - poor control


C108900 Insulin dependent diabetes maturity onset

C108911 Type I diabetes mellitus maturity onset

C108912 Type 1 diabetes mellitus maturity onset

C108A00 Insulin-dependent diabetes without complication

C108A11 Type I diabetes mellitus without complication

C108A12 Type 1 diabetes mellitus without complication

C108B00 Insulin dependent diabetes mellitus with mononeuro

C108B11 Type I diabetes mellitus with mononeuropathy

C108B12 Type 1 diabetes mellitus with mononeuropathy

C108C00 Insulin dependent diabetes mellitus with polyneuro

C108C11 Type I diabetes mellitus with polyneuropathy

C108C12 Type 1 diabetes mellitus with polyneuropathy

C108E00 Insulin dependent diabetes mellitus with hypoglyca

C108E11 Type I diabetes mellitus with hypoglycaemic coma

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C108E12 Type 1 diabetes mellitus with hypoglycaemic coma

C108F00 Insulin dependent diabetes mellitus with diabetic

C108F11 Type I diabetes mellitus with diabetic cataract

C108F12 Type 1 diabetes mellitus with diabetic cataract

C108G11 Type I diabetes mellitus with peripheral angiopath

C108G12 Type 1 diabetes mellitus with peripheral angiopath

C108H00 Insulin dependent diabetes mellitus with arthropat

C108H11 Type I diabetes mellitus with arthropathy

C108H12 Type 1 diabetes mellitus with arthropathy

C108J11 Type I diabetes mellitus with neuropathic arthropa

C108J12 Type 1 diabetes mellitus with neuropathic arthropa

C10C.12 Maturity onset diabetes in youth type 1

C10E.00 Type 1 diabetes mellitus

C10E.11 Type I diabetes mellitus

C10E.12 Insulin dependent diabetes mellitus

C10E200 Type 1 diabetes mellitus with neurological complic

C10E211 Type I diabetes mellitus with neurological complic

C10E212 Insulin-dependent diabetes mellitus with neurologi

C10E300 Type 1 diabetes mellitus with multiple complicatio

C10E311 Type I diabetes mellitus with multiple complicatio

C10E312 Insulin dependent diabetes mellitus with multiple

C10E400 Unstable type 1 diabetes mellitus

C10E411 Unstable type I diabetes mellitus

C10E412 Unstable insulin dependent diabetes mellitus

C10E500 Type 1 diabetes mellitus with ulcer

C10E511 Type I diabetes mellitus with ulcer

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C10E512 Insulin dependent diabetes mellitus with ulcer

C10E600 Type 1 diabetes mellitus with gangrene

C10E611 Type I diabetes mellitus with gangrene

C10E612 Insulin dependent diabetes mellitus with gangrene

C10E800 Type 1 diabetes mellitus - poor control

C10E811 Type I diabetes mellitus - poor control

C10E812 Insulin dependent diabetes mellitus - poor control

C10E900 Type 1 diabetes mellitus maturity onset

C10E911 Type I diabetes mellitus maturity onset

C10E912 Insulin dependent diabetes maturity onset

C10EA00 Type 1 diabetes mellitus without complication

C10EA11 Type I diabetes mellitus without complication

C10EA12 Insulin-dependent diabetes without complication

C10EB00 Type 1 diabetes mellitus with mononeuropathy

C10EB11 Type I diabetes mellitus with mononeuropathy

C10EB12 Insulin dependent diabetes mellitus with mononeuro

C10EC00 Type 1 diabetes mellitus with polyneuropathy

C10EC11 Type I diabetes mellitus with polyneuropathy

C10EC12 Insulin dependent diabetes mellitus with polyneuro

C10EE00 Type 1 diabetes mellitus with hypoglycaemic coma

C10EE11 Type I diabetes mellitus with hypoglycaemic coma

C10EE12 Insulin dependent diabetes mellitus with hypoglyca

C10EF00 Type 1 diabetes mellitus with diabetic cataract

C10EF11 Type I diabetes mellitus with diabetic cataract

C10EF12 Insulin dependent diabetes mellitus with diabetic

C10EG00 Type 1 diabetes mellitus with peripheral angiopath

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C10EG11 Type I diabetes mellitus with peripheral angiopath

C10EH00 Type 1 diabetes mellitus with arthropathy

C10EH11 Type I diabetes mellitus with arthropathy

C10EH12 Insulin dependent diabetes mellitus with arthropat

C10EJ00 Type 1 diabetes mellitus with neuropathic arthropa

C10EJ11 Type I diabetes mellitus with neuropathic arthropa

C10EK00 Type 1 diabetes mellitus with persistent proteinur

C10EK11 Type I diabetes mellitus with persistent proteinur

C10EL00 Type 1 diabetes mellitus with persistent microalbu

C10EL11 Type I diabetes mellitus with persistent microalbu

C10EM00 Type 1 diabetes mellitus with ketoacidosis

C10EM11 Type I diabetes mellitus with ketoacidosis

C10EN00 Type 1 diabetes mellitus with ketoacidotic coma

C10EN11 Type I diabetes mellitus with ketoacidotic coma

C10EQ00 Type 1 diabetes mellitus with gastroparesis

C10EQ11 Type I diabetes mellitus with gastroparesis

C10y000 Diabetes mellitus, juvenile, + other specified man

C10z000 Diabetes mellitus, juvenile type, + unspecified co

L180500 Pre-existing diabetes mellitus, insulin-dependent

C104000 Diabetes mellitus, juvenile type, with renal manif

C108000 Insulin-dependent diabetes mellitus with renal com

C108011 Type I diabetes mellitus with renal complications


C108D00 Insulin dependent diabetes mellitus with nephropat

C108D11 Type I diabetes mellitus with nephropathy

C108D12 Type 1 diabetes mellitus with nephropathy

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C10E000 Type 1 diabetes mellitus with renal complications

C10E011 Type I diabetes mellitus with renal complications

C10E012 Insulin-dependent diabetes mellitus with renal com

C10ED00 Type 1 diabetes mellitus with nephropathy

C10ED11 Type I diabetes mellitus with nephropathy

C10ED12 Insulin dependent diabetes mellitus with nephropat

C108100 Insulin-dependent diabetes mellitus with ophthalmi

C108111 Type I diabetes mellitus with ophthalmic complicat


C108700 Insulin dependent diabetes mellitus with retinopat

C108711 Type I diabetes mellitus with retinopathy


C10E100 Type 1 diabetes mellitus with ophthalmic complicat

C10E111 Type I diabetes mellitus with ophthalmic complicat

C10E112 Insulin-dependent diabetes mellitus with ophthalmi

C10E700 Type 1 diabetes mellitus with retinopathy

C10E711 Type I diabetes mellitus with retinopathy

C10E712 Insulin dependent diabetes mellitus with retinopat

C10EP00 Type 1 diabetes mellitus with exudative maculopath

C10EP11 Type I diabetes mellitus with exudative maculopath

CKD

1Z12.00 Chronic kidney disease stage 3

1Z15.00 Chronic kidney disease stage 3A

1Z16.00 Chronic kidney disease stage 3B

1Z1B.00 Chronic kidney disease stage 3 with proteinuria

1Z1B.11 CKD stage 3 with proteinuria

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1Z1C.00 Chronic kidney disease stage 3 without proteinuria

1Z1C.11 CKD stage 3 without proteinuria

1Z1D.00 Chronic kidney disease stage 3A with proteinuria

1Z1D.11 CKD stage 3A with proteinuria

1Z1E.00 Chronic kidney disease stage 3A without proteinuria

1Z1E.11 CKD stage 3A without proteinuria

1Z1F.00 Chronic kidney disease stage 3B with proteinuria

1Z1F.11 CKD stage 3B with proteinuria

1Z1G.00 Chronic kidney disease stage 3B without proteinuria

1Z1G.11 CKD stage 3B without proteinuria

K053.00 Chronic kidney disease stage 3

1Z1H.00 Chronic kidney disease stage 4 with proteinuria

1Z1H.11 CKD stage 4 with proteinuria

1Z1J.00 Chronic kidney disease stage 4 without proteinuria

1Z1J.11 CKD stage 4 without proteinuria


1Z1K.00 Chronic kidney disease stage 5 with proteinuria

1Z1K.11 CKD stage 5 with proteinuria

1Z1L.00 Chronic kidney disease stage 5 without proteinuria

1Z1L.11 CKD stage 5 without proteinuria

7L1A.11 Dialysis for renal failure

7L1A000 Renal dialysis

7L1A100 Peritoneal dialysis

7L1A200 Haemodialysis NEC

7L1A400 Automated peritoneal dialysis

7L1A500 Continuous ambulatory peritoneal dialysis

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7L1A600 Peritoneal dialysis NEC


SP06B00 Continuous ambulatory peritoneal dialysis associated perit

SP0E.00 Disorders associated with peritoneal dialysis

K05..12 End stage renal failure

K050.00 End stage renal failure

ACS, acute coronary syndrome; ASCVD, atherosclerotic cardiovascular disease; CHD, coronary heart

disease; CKD, chronic kidney disease; PAD, peripheral arterial disease; T1DM, type 1 diabetes mellitus;

T2DM, type 1 diabetes mellitus

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SUPPLEMENTAL TABLE S2. Categorisation of Lipid Modifying Therapy (LMT)

High-intensity statin Atorvastatin 20, 40, and 80 mg; rosuvastatin 10, 20, and 40 mg; simvastatin 80

mg

Medium-intensity statin Atorvastatin 10 mg; rosuvastatin 5 mg; simvastatin 20 and 40 mg; fluvastatin

80 mg

Low-intensity statin Simvastatin 10 mg; pravastatin 10, 20, and 40 mg; fluvastatin 20 and 40 mg

Nonstatin LMT Ezetimibe, nicotinic acid (niacin, acipimox), fibrates (benzafibrate, ciprofibrate,

fenofibrate, and gemfibrozil), bile acid sequestrants (cholestyramine,

colesevelam, and colestipol)

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SUPPLEMENTAL TABLE S3. Baseline Characteristics for the Overall ASCVD

Cohort and Prevalent Subgroups

Recent ACS

(n = 3112)

Other CHD (n = 60 347)

Ischaemic stroke / TIA (n = 26 146)

PAD (n = 19 830)

Total ASCVD

(n = 91 479)


Age, mean, years (SD) 67.8 (12.8) 72.6 (10.6) 73.9 (11.5) 73.5 (10.3) 72.6 (10.9)

Male, % 66.5 63.7 52.3 65.4 60.7


2.7 (1.4)

2.7 (1.4)

2.6 (1.4)

2.8 (1.4)

2.7 (1.4)

Ethnicity, %

White 28.3 30.3 29.5 30.6 30.0

South Asian† 15.1 14.0 13.8 12.9 13.9

Black Caribbean / African

0.3 0.3 0.5 0.4 0.3

Chinese 0.0 0.1 0.1 0.1 0.1

Not recorded 56.4 55.4 56.1 56.1 55.8

Current smoker, % 15.2 12.1 13.5 26.6 14.1

BMI, mean, kg/m2 (SD) 28.4 (5.4) 28.5 (5.3) 27.8 (5.4) 27.7 (5.3) 28.3 (5.4)

Systolic BP, mean (SD)

128.9 (17.8)

131.4 (15.8)

132.8 (16.0)

133.5 (16.4)

132.1 (15.9)


Recent ACS, % 100.0 3.3 0.9 1.6 3.4

Other CHD, % 64.2 100.0 24.0 34.0 66.0

Ischaemic stroke / TIA, %

7.6 10.4 100.0 21.5 28.6

PAD, % 10.1 11.2 16.3 100.0 21.7

DM, % 27.0 30.0 27.3 34.5 29.4

Hypertension, % 50.4 61.2 64.0 66.7 61.5

History of CHF, % 14.0 11.3 6.9 8.9 9.1

CKD stage III 17.2 24.4 22.1 23.0 23.5

CKD stage IV- V‡ 0.2 0.3 0.2 0.4 0.2

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Beta-blockers, % 81.4 60.1 23.5 22.4 48.7

ACEI/ARBs, % 85.0 65.3 52.1 52.4 61.7

Antiplatelets,# % 52.5 13.5 29.7 15.4 18.5

* Social deprivation index is defined by Townsend deprivation index score, 1 = most affluent and 5 = least

affluent;

† Includes Indian, Pakistani, Bangladeshi, and other South Asian individuals;

‡ Stage V CKD includes

end-stage renal disease and dialysis. ¶ Medication use on index date.

# Clopidogrel/ticagrelor/prasugrel

ACEI, angiotensin converting enzyme inhibitor; ACS, acute coronary syndrome; ARB, angiotensin II

receptor blocker; ASCVD, atherosclerotic cardiovascular disease; BMI, body-mass index; BP, blood

pressure; CHD, coronary heart disease; CHF, congestive heart failure; CKD, chronic kidney disease; DM,

diabetes mellitus; PAD, peripheral arterial disease; SD, standard deviation; TIA, transient ischaemic

attack

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SUPPLEMENTAL TABLE S4. Use of LMT in the Overall ASCVD Cohort and

Prevalent Subgroups

Recent ACS

(n = 3112)



PAD (n = 19 830)

Total ASCVD

(n = 91 479)

High-intensity statin, % 62.4 35.5 24.7 30.2 31.4

Monotherapy, % 93.3 91.9 92.6 91.1 92.2

Plus Ezetimibe, % 1.0 4.5 3.5 4.7 4.1

Plus other nonstatin LMT, % 5.8 3.5 3.9 4.2 3.7

Medium-intensity statin, % 22.6 40.7 44.8 42.8 42.1

Monotherapy, % 98.6 97.9 98.4 98.4 98.2

Plus Ezetimibe, % 0.6 1.2 0.9 0.8 1.0


Low-intensity statin, % 2.1 5.7 5.8 5.4 5.6

Monotherapy, % 93.8 95.8 96.6 96.3 96.3

Plus Ezetimibe, % 6.3 3.3 2.6 3.0 2.8


Nonstatins only, % 0.9 2.0 1.8 1.9 1.9

Ezetimibe, monotherapy, % 70.4 61.5 65.4 60.1 61.6

Other nonstatin LMT, % 29.6 38.5 34.6 39.9 38.4

Not currently treated by LMT, % 12.1 16.0 22.9 19.7 19.0


20.7 16.7 10.1 12.7 13.2


22.8 40.5 38.9 36.7 38.4


5.6 9.9 7.7 7.6 8.5

Previously on nonstatin LMT, % 4.8 7.2 5.6 5.7 5.9

No previous LMT, % 46.1 25.7 37.7 37.3 34.0

Numbers in the grey bars denote absolute percentages, and add up to 100% vertically. Numbers in the

white bars are relative percentages of the absolute percentages in the grey bars.


disease; LMT, lipid modifying therapy; PAD, peripheral arterial disease; TIA, transient ischaemic attack

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SUPPLEMENTAL TABLE S5. Lipid Level Achievement by LMT in the Overall

ASCVD Cohort and Prevalent Subgroups

Recent ACS

(n = 3112)



PAD (n = 10 234)

Total ASCVD

(n = 91 479)

Mean LDL-C, mmol/L

High-intensity statin 1.8 2.1 2.1 2.1 2.1

Medium-intensity statin 2.0 2.0 2.0 2.1 2.0

Low-intensity statin 2.5 2.3 2.4 2.4 2.3

Nonstatin LMT only 3.0 3.0 3.0 3.0 3.0

No current LMT 2.9 3.1 3.1 3.1 3.1

Total 2.0 2.2 2.3 2.4 2.3

LDL-C <1.8 mmol/L, %





No current LMT 14.9 8.7 6.5 7.4 8.0

Total 43.9 31.5 27.9 26.4 30.6

Mean non-HDL-C, mmol/L





No current LMT 3.6 3.7 3.8 3.8 3.8

Total 2.6 2.9 3.0 3.1 2.9

Non-HDL-C <2.6 mmol/L, %





No current LMT 20.7 14.9 13.8 13.6 14.5

Total 54.8 42.6 41.0 36.9 42.0


disease; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LMT,

lipid modifying therapy; PAD, peripheral arterial disease; TIA, transient ischaemic attack

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ASCVD Cohort and Hierarchical Subgroups

Recent ACS

(n = 3112)



PAD (n = 19 830)

Total ASCVD

(n = 91 479)

Mean LDL-C, mmol/L





No current LMT 2.9 3.1 3.1 3.1 3.1

Total 2.0 2.2 2.3 2.3 2.3






No current LMT 14.9 8.9 7.0 8.4 8.0

Total 43.8 32.0 28.4 26.4 30.6






No current LMT 3.6 3.7 3.8 3.7 3.8

Total 2.6 2.9 3.0 3.0 2.9






No current LMT 20.7 15.0 14.3 14.9 14.5

Total 54.5 43.0 41.5 36.9 42.0




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SUPPLEMENTAL TABLE S7. Lipid Level Achievement by LMT in the Overall Non-

ASCVD Cohort and Subgroups

T2DM and QRISK2

>10% with CKD

(n = 11 102)

T2DM and QRISK 2

>10% without

CKD (n = 52

556)

T1DM and age >40

years with CKD

(n = 749)

T1DM and age >40 years

without CKD

(n = 4204)

CKD without

DM criteria (n = 23

475)

Total non-ASCVD (n = 92

086)

Mean LDL-C, mmol/L

High-intensity statin 2.0 2.1 1.9 2.1 2.2 2.1

Medium-intensity statin 1.9 2.0 1.8 2.0 2.2 2.0

Low-intensity statin 2.1 2.3 2.0 2.3 2.5 2.3

Nonstatin LMT only 2.8 2.9 2.5 2.7 3.1 2.9

No current LMT 2.9 3.0 2.7 2.7 3.3 3.1

Total 2.2 2.4 2.1 2.3 2.8 2.4






No current LMT 10.3 7.5 17.6 11.5 3.7 6.7

Total 35.7 28.4 39.8 25.9 15.7 26.0






No current LMT 3.6 3.8 3.3 3.2 3.9 3.8

Total 2.94 3.1 2.7 2.9 3.4 3.2






No current LMT 16.1 12.1 26.8 26.2 8.5 11.9

Total 41.9 34.3 52.0 43.2 24.3 33.2

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ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; HDL-C, high-density

lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LMT, lipid modifying therapy; T1DM,

type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus

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The RECORD statement – checklist of items, extended from the STROBE statement, that should be reported in observational studies using

routinely collected health data.

Item

No.

STROBE items Location in

manuscript where

items are reported

RECORD items Location in

manuscript

where items are

reported

Title and abstract

1 (a) Indicate the study’s design

with a commonly used term in

the title or the abstract (b)

Provide in the abstract an

informative and balanced

summary of what was done and

what was found

Abstract p3

RECORD 1.1: The type of data used

should be specified in the title or

abstract. When possible, the name of

the databases used should be included.

RECORD 1.2: If applicable, the

geographic region and timeframe within

which the study took place should be

reported in the title or abstract.

RECORD 1.3: If linkage between

databases was conducted for the study,

this should be clearly stated in the title

or abstract.

Abstract p3

Abstract p3

Not applicable

(n/a)

Introduction

Background

rationale

2 Explain the scientific background

and rationale for the investigation

being reported

Intro p5/6 Intro p5/6

Objectives 3 State specific objectives,

including any prespecified

hypotheses


Methods

Study Design 4 Present key elements of study

design early in the paper

Methods p7-11 Methods p7-11

Setting 5 Describe the setting, locations,

and relevant dates, including

periods of recruitment, exposure,

follow-up, and data collection


Participants 6 (a) Cohort study - Give the

eligibility criteria, and the

Methods p7-11 plus

supplemental files

RECORD 6.1: The methods of study

population selection (such as codes or

Methods p7-11

plus supplemental

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sources and methods of selection

of participants. Describe methods

of follow-up

Case-control study - Give the


sources and methods of case

ascertainment and control

selection. Give the rationale for

the choice of cases and controls

Cross-sectional study - Give the



of participants

(b) Cohort study - For matched

studies, give matching criteria

and number of exposed and

unexposed

Case-control study - For matched


and the number of controls per

case

algorithms used to identify subjects)

should be listed in detail. If this is not

possible, an explanation should be

provided.

RECORD 6.2: Any validation studies

of the codes or algorithms used to select

the population should be referenced. If

validation was conducted for this study

and not published elsewhere, detailed

methods and results should be provided.

RECORD 6.3: If the study involved

linkage of databases, consider use of a

flow diagram or other graphical display

to demonstrate the data linkage process,

including the number of individuals

with linked data at each stage.

files

Supplement

n/a

Variables 7 Clearly define all outcomes,

exposures, predictors, potential

confounders, and effect

modifiers. Give diagnostic

criteria, if applicable.

Methods p7-11 plus

supplemental files

RECORD 7.1: A complete list of codes

and algorithms used to classify

exposures, outcomes, confounders, and

effect modifiers should be provided. If

these cannot be reported, an explanation

should be provided.

Supplement

Data sources/

measurement

8 For each variable of interest, give

sources of data and details of

methods of assessment

(measurement).

Describe comparability of

assessment methods if there is

more than one group


Bias 9 Describe any efforts to address

potential sources of bias

Addressed in Results

p15 and Discussion

p21

Addressed in

Results p15 and

Discussion p21

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Study size 10 Explain how the study size was

arrived at


Quantitative

variables

11 Explain how quantitative

variables were handled in the

analyses. If applicable, describe

which groupings were chosen,

and why


Statistical

methods

12 (a) Describe all statistical

methods, including those used to

control for confounding

(b) Describe any methods used to

examine subgroups and

interactions

(c) Explain how missing data

were addressed

(d) Cohort study - If applicable,

explain how loss to follow-up

was addressed

Case-control study - If

applicable, explain how matching

of cases and controls was

addressed

Cross-sectional study - If

applicable, describe analytical

methods taking account of

sampling strategy

(e) Describe any sensitivity

analyses

Methods p7-11, with

specific stats

methods on p10-11.

Methods p7-11,

with specific stats

methods on p10-

11.

Data access and

cleaning methods

.. P10, patient

involvement section

RECORD 12.1: Authors should

describe the extent to which the

investigators had access to the database

population used to create the study

population.

RECORD 12.2: Authors should provide

information on the data cleaning

methods used in the study.

P10, patient

involvement

section

As above

Linkage .. n/a RECORD 12.3: State whether the study n/a

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included person-level, institutional-

level, or other data linkage across two

or more databases. The methods of

linkage and methods of linkage quality

evaluation should be provided.

Results

Participants 13 (a) Report the numbers of

individuals at each stage of the

study (e.g., numbers potentially

eligible, examined for eligibility,

confirmed eligible, included in

the study, completing follow-up,

and analysed)

(b) Give reasons for non-

participation at each stage.

(c) Consider use of a flow

diagram

P12 and Figure 2 RECORD 13.1: Describe in detail the

selection of the persons included in the

study (i.e., study population selection)

including filtering based on data

quality, data availability and linkage.

The selection of included persons can

be described in the text and/or by means

of the study flow diagram.

P12 and Figure 2

Descriptive data 14 (a) Give characteristics of study

participants (e.g., demographic,

clinical, social) and information

on exposures and potential

confounders

(b) Indicate the number of

participants with missing data for

each variable of interest

(c) Cohort study - summarise

follow-up time (e.g., average and

total amount)

P12 P12

Outcome data 15 Cohort study - Report numbers of

outcome events or summary

measures over time

Case-control study - Report

numbers in each exposure

category, or summary measures

of exposure

Cross-sectional study - Report

numbers of outcome events or

summary measures

P12-15 P12-15

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Main results 16 (a) Give unadjusted estimates

and, if applicable, confounder-

adjusted estimates and their

precision (e.g., 95% confidence

interval). Make clear which

confounders were adjusted for

and why they were included

(b) Report category boundaries

when continuous variables were

categorized

(c) If relevant, consider

translating estimates of relative

risk into absolute risk for a

meaningful time period

P12-15 Results p12-15

Other analyses 17 Report other analyses done—e.g.,

analyses of subgroups and

interactions, and sensitivity

analyses

Results p12-15 Results p12-15

Discussion

Key results 18 Summarise key results with

reference to study objectives

P16 P16

Limitations 19 Discuss limitations of the study,

taking into account sources of

potential bias or imprecision.

Discuss both direction and

magnitude of any potential bias

P20 RECORD 19.1: Discuss the

implications of using data that were not

created or collected to answer the

specific research question(s). Include

discussion of misclassification bias,

unmeasured confounding, missing data,

and changing eligibility over time, as

they pertain to the study being reported.

P20

Interpretation 20 Give a cautious overall

interpretation of results

considering objectives,

limitations, multiplicity of

analyses, results from similar

studies, and other relevant

evidence

P16-20, summary on

p21

P16-20, summary

on p21

Generalisability 21 Discuss the generalisability

(external validity) of the study

P16-21 P16-21

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results

Other Information

Funding 22 Give the source of funding and

the role of the funders for the

present study and, if applicable,

for the original study on which

the present article is based

P22 P22

Accessibility of

protocol, raw

data, and

programming

code

.. Information provided

within supplement


information on how to access any

supplemental information such as the

study protocol, raw data, or

programming code.

Information

provided within

supplement

*Reference: Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, Sørensen HT, von Elm E, Langan SM, the RECORD Working

Committee. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLoS Medicine 2015;

in press.

*Checklist is protected under Creative Commons Attribution (CC BY) license.

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A Retrospective Examination of Lipid-Lowering Treatment Patterns in a Real-World High-Risk Cohort in UK in 2014:

Comparison with the National Institute for Health and Care Excellence (NICE) 2014 Lipid Modification Guidelines

Journal: BMJ Open

Manuscript ID bmjopen-2016-013255.R1

Article Type: Research

Date Submitted by the Author: 15-Dec-2016

Complete List of Authors: Steen, Dylan; University of Cincinnati College of Medicine, Division of CV Health and Disease, UC Heart, Lung, and Vascular Institute, University of Cincinnati College of Medicine Khan, Irfan; Sanofi, Global Health Economics and Outcomes Research Ansell, David; IMS Health Sanchez, Robert; Regeneron Pharmaceuticals Inc. , Global Health Economics and Outcomes Research Ray, Kausik; Imperial College London, Department of Primary Care and Public Health

<b>Primary Subject

Heading</b>: Cardiovascular medicine

Secondary Subject Heading: Cardiovascular medicine



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A Retrospective Examination of Lipid-Lowering Treatment

Patterns in a Real-World High-Risk Cohort in UK in 2014:

Comparison with the National Institute for Health and Care

Excellence (NICE) 2014 Lipid Modification Guidelines

Dylan Steen,1 Irfan Khan,2 David Ansell,3 Robert J. Sanchez,4 Kausik K. Ray5

1Division of Cardiovascular Health and Disease, University of Cincinnati College of

Medicine, Cincinnati, OH, USA

2Global Health Economics and Outcomes Research, Sanofi, Bridgewater, NJ, USA

3IMS Health, London, UK

4Global Health Economics and Outcomes Research, Regeneron Pharmaceuticals Inc.,

Tarrytown, NY, USA

5Department of Primary Care and Public Health, Imperial College, London, UK

Correspondence to:

Dylan Steen

Director of Clinical Trials and Population Health Research

Division of CV Health and Disease

UC Heart, Lung, and Vascular Institute, University of Cincinnati College of Medicine

Cardiovascular Center, 231 Albert Sabin Way, Cincinnati, OH 45267

Tel: (908) 208-6927; Fax: (513) 558-4545; Email: [email protected]

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Word count: 4308 (main body of the article)

Keywords: low-density lipoprotein cholesterol (LDL-C), lipids, guidelines, cardiovascular

disease, statins

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ABSTRACT

Background: In 2014, guidelines from the National Institute for Health and Care

Excellence (NICE) provided updated recommendations on lipid-modifying therapy

(LMT). We assessed clinical practice contemporaneous to release of these guidelines in

a UK general-practice setting for secondary and high-risk primary-prevention

populations, and extrapolated the findings to UK nation-level.

Methods: Patients from The Health Improvement Network database with the following

criteria were included: lipid profile in 2014 (index date); ≥20 years of age; ≥2 years

representation in database prior to index; ≥1 statin indication either for atherosclerotic

cardiovascular disease (ASCVD) or the non-ASCVD conditions high-risk diabetes

mellitus and/or chronic kidney disease.

Results: Overall, 183565 patients met the inclusion criteria (n=91479 for ASCVD, 92086

for non-ASCVD). In those with ASCVD, 79% received statin treatment and 31%

received high-intensity statin. In the non-ASCVD group, 62% were on a statin and 57%

received medium- or high-intensity statin. In the ASCVD and non-ASCVD cohorts, 6%

and 15%, respectively, were already treated according to dosing recommendations as

per updated NICE guidelines. Extrapolation to the 2014 UK population indicated that, of

the 3.3 million individuals with ASCVD, 2.4 million would require statin up-titration and

680000 would require statin initiation (31% de-novo initiation, 60% re-initiation, 9%

addition to non-statin LMT) to achieve full concordance with updated guidelines. Of the

3.5 million high-risk non-ASCVD individuals, 1.6 million would require statin up-titration

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and 1.4 million would require statin initiation (59% de-novo initiation, 36% re-initiation,

5% addition to non-statin LMT).

Conclusions: A large proportion of UK individuals with ASCVD and high-risk non-

ASCVD received statin treatment (79% and 62%, respectively) during the year of NICE

2014 guidelines release. Up to 94% of ASCVD patients and 85% of high-risk non-

ASCVD individuals, representing approximately 3 million individuals in each group,

would require statin up-titration or initiation to achieve full concordance with updated

guidelines.

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Strengths and limitations of this study

� Potential implications of the 2014 NICE lipid-modification therapy guidelines on

clinical practice in UK have not been evaluated in prior reports.

� We analysed a cohort of high-risk patients representing the UK general practice from

a large representative data source and developed estimates of the extrapolated

number of individuals across the UK, including subgroups of interest, whose

treatment was already concordant with the new guidelines and those for whom up-

titration or initiation of statin therapy would be needed to achieve full concordance.

� Our study provides novel data on clinical practice in many high-risk subgroups such

as those with ischaemic stroke, peripheral arterial disease, diabetes without vascular

disease, and chronic kidney disease.

� A limitation of the study is that the summary demographic and clinical characteristics

of the cohort were based on information available in the database; certain data such

as body-mass index, ethnicity, blood pressure, and smoking status were not

available for all patients.

� Another limitation of the study is that though the definition of medication utilisation

was optimised to provide valid point-in-time estimates concurrent with lipid

measurements, whether patients actually took their medications as prescribed

cannot be ensured from the data source.

� The aim of the study was to provide a comparison of 2014 clinical practice relative to

guidelines released in 2014; these results cannot be interpreted in terms of the

impact of the new guidelines on clinical practice.

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Introduction

Despite a decade of continuing decline in cardiovascular (CV) disease mortality, CV

deaths remain the leading cause of mortality in the UK, accounting for approximately

31% of all deaths, with ischaemic heart disease and stroke representing the vast

majority (17% and 10%, respectively).1,2 Reducing low-density lipoprotein cholesterol

(LDL-C) with statin therapy has been shown to reduce all-cause and CV mortality, as

well as CV outcomes such as non-fatal myocardial infarction (MI), coronary

revascularisation procedures, and non-fatal ischaemic stroke in populations with prior

atherosclerotic CV disease (ASCVD) and in certain primary-prevention populations.3,4

The high tolerability and safety of statins have also been established across these

subgroups.3-5 Despite this, appropriate statin use and atherogenic lipid level reduction

remain suboptimal in clinical practice.6

Statins are recommended by the National Institute for Health and Care Excellence

(NICE) as first-line lipid modifying therapy (LMT) for the reduction of CV event risk in

patients with ASCVD as well as diabetes mellitus (DM), familial hypercholesterolaemia,

chronic kidney disease (CKD), and other high-risk primary-prevention populations.7 In

line with evidence from randomised trials and the recent availability of generic

atorvastatin, the 2014 NICE guidelines recommend more intensive statin therapy

compared to the 2008 guidelines. The recommended regimens include atorvastatin 80

mg for patients with ASCVD and atorvastatin 20 mg or higher for those with most other

high-risk conditions; although lower doses of atorvastatin can be used in cases of

potential drug to drug interactions, high risk of adverse effects, or patient preference.

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The present study assessed real world clinical practice in 2014 relative to the

updated NICE guidelines. In a large, representative UK population, we analysed LMT

utilisation for each of the following indications: recent acute coronary syndrome (ACS),

other coronary heart disease (CHD), ischaemic stroke / transient ischaemic attack (TIA),

peripheral arterial disease (PAD), type 1 (T1) DM, type 2 (T2) DM, and CKD. We

provide an estimate of the extrapolated number of individuals in the UK within each

subgroup whose treatment was already concordant with the guidelines as well as those

for whom up-titration or initiation of statin therapy would be needed for full concordance.

For the same patient subgroups, we also evaluated achievement of LDL-C and non-

high-density lipoprotein cholesterol (non-HDL-C) goals as defined by the 2011

European Society of Cardiology (ESC) / European Atherosclerosis Society (EAS) lipid

management guidelines.8

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Methods

This study was based on a retrospective, cross-sectional, and observational cohort. It

was approved by the Scientific Review Committee, an independent UK-based ethics

committee established to review studies from The Health Improvement Network (THIN).

Database and cohort selection

We utilised the THIN database, which represents anonymised patient records from

general practitioners (GPs) in the UK. As of the end of 2014, the database represented

422 active GP practices and 3.5 million unique active patients. The THIN database has

been found to be broadly representative of the UK population, and the validity of

recorded information has been established in previous studies,9,10 including the validity

of utilising Read codes to identify ASCVD, other high CV risk conditions, and incident

CV events.11,12 Due to the extensive use of GP electronic prescribing in the UK, the

recording of prescriptions is expected to be both complete and accurate.13 Furthermore,

the scope of THIN data to inform complex epidemiological observations was supported

by the validation of the updated QRISK2 model for estimating the 10-year incident risk

of CV disease in the UK general population.14

The following inclusion criteria were utilised: presence of a lipid profile

measurement in 2014 (last LDL-C measurement in 2014 was considered the index

date); ≥20 years of age; and presence of ≥1 high CV risk condition for which statins

would be recommended as per NICE guidelines (see below). In order to ensure

complete capture of pertinent demographic and clinical characteristics, and to assess

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for prior statin use among those not currently treated with statins, we also required

continuous representation in the database for ≥2 years prior to the index date.

Determination of ASCVD and non-ASCVD categories

NICE 2014 guidelines recommend statin treatment in following groups: 1) ASCVD,

where atorvastatin 80 mg is recommended; 2) T2DM with QRISK2 10-year risk ≥10%,

where atorvastatin 20 mg is recommended; 3) T1DM with age >40 years or DM duration

of >10 years or presence of nephropathy or other CV risk factors, where atorvastatin 20

mg is recommended; 4) CKD, where atorvastatin 20 mg is recommended; and 5) all

other individuals with QRISK2 10-year risk ≥10%, where atorvastatin 20 mg is

recommended. Our overall study cohort represents groups 1–4 (excluding 5), with

group 1 representing the ASCVD population and groups 2–4 representing a high-risk

non-ASCVD population.

ASCVD and non-ASCVD conditions were identified using standardised Read codes

(see supplemental table S1) as follows: 1) recent ACS (MI or unstable angina within 12

months prior to index date); 2) other CHD (e.g. ACS >12 months prior to index date, any

coronary revascularisation, stable angina, or ischaemic cardiomyopathy); 3) ischaemic

stroke or TIA; 4) PAD (presence of revascularisation/surgery for significant peripheral

arterial, aortic, or carotid disease); 5) T2DM with QRISK2 10-year risk ≥10%; 6) T1DM

with age >40 years (represents a slight simplification of guideline criteria with application

of only the age limit); and 7) CKD stage III-V (estimated glomerular filtration rate <60

mL/min/1.73 m2 or dialysis, herewith referred to as “CKD”). A thorough process

involving clinical cardiology and coding expert review was undertaken to optimise the

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specificity of Read codes for each condition. Read codes were also used to identify non-

CV comorbidities. The QRISK2 10-year risk was estimated for individuals with T2DM in

the non-ASCVD cohort via application of the algorithm to patient-level data (details

available in Supplementary Appendix).14

Patients with conditions 1-4 were collectively referred to as “ASCVD”, while those

with only conditions 5-7 were collectively referred to as “non-ASCVD”. Those with

ASCVD were categorised hierarchically (as above) into four mutually exclusive groups:

1) recent ACS; 2) other CHD; 3) ischaemic stroke/TIA; and 4) PAD. A sensitivity

analysis was also conducted by categorising these same patients by each condition

present, referred to as prevalent disease categorisation. As an example, an individual

with a history of elective coronary revascularisation and PAD would be categorised

hierarchically as “other CHD,” but as both “other CHD” and “PAD” under the prevalent

disease categorisation. Non-ASCVD patients were categorised into five mutually

exclusive categories to better evaluate the association of specific conditions with LMT

utilisation and lipid goal achievement. These categories were: 1) T2DM and QRISK2

≥10% with CKD; 2) T2DM and QRISK2 ≥10% without CKD; 3) T1DM and age >40

years with CKD; 4) T1DM and age >40 years without CKD; and 5) other CKD not

meeting the criteria of the other categories. For enhanced readability, we omitted the

qualifier QRISK2 10-year risk ≥10% from the non-ASCVD T2DM population, and age

>40 years from the non-ASCVD T1DM population, considering them implicit in the

definitions. The fifth category was referred to as “CKD alone”.

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Determination of medication treatment

For any particular medication, patients were considered to have been treated on the

index date if the medication supply via a recorded prescription was present on or within

30 days prior to the index date, regardless of the duration of the prescription (fig 1). This

point-in-time assessment approach was utilised to better control for factors such as

discontinuation over time. In addition, this also ensured that lipid levels best reflected

the impact of the treatment regimen as the assessment of both measures was

concurrent. Those not treated on the index date but with evidence of a prior recorded

prescription were considered to have a history of being treated. Those without any

evidence of a recorded prescription for a medication within the 2 years prior to the index

date were considered to have no documented history of being treated. LMT was

categorised as high-, medium-, and low-intensity statin therapy, as well as non-statin

therapy (supplemental table S2).7

We also summarised statin utilisation as per 2014 NICE guideline

recommendations, which recommend treatment with atorvastatin 80 mg and 20 mg in

ASCVD and non-ASCVD patients, respectively (for our study we interpreted this as

regimens of equivalent or higher potency: atorvastatin 80 mg equivalent or higher

[atorvastatin 80 mg, rosuvastatin 40 mg]; and atorvastatin 20 mg equivalent or higher

[atorvastatin 20, 40 and 80 mg, rosuvastatin 10, 20 and 40 mg, and simvastatin 80 mg]).

It should be noted, however, that guidelines allow for a consideration of a lower dose of

atorvastatin in presence of drug interactions, risk of adverse effects, or patient

preference. Statin categories included statins administered as either monotherapy or in

combination with ≥1 non-statin medications.

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Determination of LDL-C and non-HDL-C levels

We assessed the achievement of LDL-C and non-HDL-C levels relative to the ESC/EAS

2011 guidelines. They recommend goals of LDL-C <1.8 mmol/L (70 mg/dL) and non-

HDL-C <2.6 mmol/L (100 mg/dL) for both the ASCVD and non-ASCVD populations

reported in the current study.8

Patient Involvement

Our study was based on an analysis of patient-level data represented in an electronic

medical record (EMR) database utilized by a set of GPs in UK utilizing the Vision EMR

software. In order to protect patient privacy, the analyses reported in our study are

based on de-identified version of the database where patient identifiers are encrypted

such that it is not possible to link an individual patient in the dataset to a specific

individual in the real-world. As such, our study did not involve any direct patient-level

interaction.

Statistical analyses

All statistical analyses were descriptive in nature. Cohort characteristics, LMT utilisation,

and achieved LDL-C and non-HDL-C levels were summarised via proportions and mean

± standard deviation (SD) as appropriate. Findings on number of patients treated with

LMT were extrapolated to the UK population via an adjusted extrapolation methodology

that accounted for differential weights by clinical and demographic profiles (details

available in Supplementary Appendix). All analyses were conducted with SAS® software

version 9.4.

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Results

The inclusion criteria were met by 183 565 patients, of whom approximately one-half

(n=91 479) had established ASCVD, with the remainder (n=92 086) having non-ASCVD

high-risk conditions (fig 2). According to hierarchical disease categorisation for the

ASCVD group, 3% had a recent ACS, 64% had another CHD diagnosis, 22% had a

history of ischaemic stroke/TIA, and 11% had PAD. Approximately one-third of the

ASCVD cohort had concomitant DM; and close to one-fourth had concomitant CKD.

Baseline characteristics of the ASCVD group by hierarchical categorisation are

presented in table 1 and by prevalent categorisation in supplemental table S3. Baseline

characteristics for the non-ASCVD group are also presented in table 1. In the non-

ASCVD group, 12% had T2DM with CKD; 57% had T2DM without CKD; 1% had T1DM

with CKD; 5% had T1DM without CKD; and 25% had CKD alone.

LMT utilisation in 2014

ASCVD population

Approximately 79% of the ASCVD population received treatment with a statin on the

index date (table 2). By hierarchical categories, statin use was 87% in the recent ACS

group, 82% in the other CHD group, and 73% in both the ischaemic stroke/TIA and PAD

groups. Of patients currently treated with statins, 40% were receiving treatment with

high-intensity statins (defined as per supplementary table S2): 72% for recent ACS,

42% for other CHD, 32% for PAD, and 29% for ischaemic stroke/TIA. Statins were

predominantly used as monotherapy: 92% for high-intensity statins, 98% for medium-

intensity statins, and 96% for low-intensity statins. Of patients not currently treated with

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LMT, 34% had no evidence of any LMT treatment in the 2 years prior to the index date.

LMT utilisation by prevalent categorisation in the ASCVD group is presented in

supplemental table S4.


In the non-ASCVD population, 62% received treatment with a statin on the index date

(table 2). In the subgroups, statin use was 71% in T2DM with CKD, 66% in T2DM

without CKD, 73% in the T1DM with CKD, 62% in T1DM without CKD, and 49% in CKD

alone. Of the patients receiving statins, at least a medium-intensity statin was utilised in

92%. As with ASCVD patients, statins were most commonly used as monotherapy: 93%

for high-intensity statins and 98% for both medium- and low-intensity statins. Of patients

not currently treated with LMT, 62% had no evidence of any LMT treatment in the 2

years prior to the index date.

Comparison of LMT utilisation in 2014 with 2014 NICE recommendations

ASCVD population

Statin treatment already concordant with the NICE 2014 guidelines (atorvastatin 80 mg

equivalent or higher; which is a subset of statins regarded as high-intensity) was

observed in 6% of the ASCVD cohort, with 73% treated with a less-intensive statin

regimen than recommended and 21% not treated with any statin (table 3). Extrapolated

to the UK ASCVD population, this identified approximately 202 000 individuals whose

treatment was already concordant with the updated guidelines, 2.4 million who would

require statin up-titration, and 680 000 in whom statin initiation would be recommended

to achieve full concordance. For those requiring statin initiation, 31% represented a

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need for de-novo initiation, 60% re-initiation due to past discontinuation, and 9% statin

addition to non-statin LMT. NICE 2014 guidelines recommended statin therapy was

most commonly used in patients with a recent ACS (33%) and the least used in patients

with history of an ischaemic stroke/TIA or PAD (2% each).


Statin treatment already concordant with the NICE 2014 guidelines (atorvastatin 20mg

equivalent or higher) was observed in 15% of the non-ASCVD cohort, with 47% treated

with a less-intensive statin regimen than recommended and 37% not treated with any

statin (table 3). Extrapolation identified approximately 508 000 UK non-ASCVD patients

(i.e. fulfilling the DM and/or CKD indications) whose treatment was already concordant

with the updated guidelines, 1.6 million who require up-titration, and 1.4 million in whom

statin initiation would be recommended to achieve full concordance. For those requiring

statin initiation, 59% represented a need for de-novo initiation, 36% re-initiation due to

past discontinuation, and 5% statin addition to non-statin LMT. Of the subgroups, T1DM

with CKD was most likely to already be receiving NICE 2014 guidelines recommended

statin therapy (26%) and CKD alone was least likely (10%).

ESC/EAS-recommended lipid goal achievement

ASCVD population

The mean LDL-C was 2.3 mmol/L with approximately 31% achieving a LDL-C <1.8

mmol/L. Mean non-HDL-C was 2.9 mmol/L with approximately 42% achieving a non-

HDL-C <2.6 mmol/L. Supplemental tables S5 and S6 provide a detailed summary of the

mean LDL-C and non-HDL-C levels, achievement of LDL-C <1.8 mmol/L and non-HDL-

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C <2.6 mmol/L, by LMT treatment for prevalent and hierarchical subgroups.

Achievement of LDL-C and non-HDL-C goals was associated with the hierarchy of

ASCVD subgroups, with recent ACS being the highest and PAD being the lowest.

Patients with recent ACS receiving high-intensity statins had the highest achievement of

both lipid goals: LDL-C <1.8 mmol/L was 53% and non-HDL-C <2.6 mmol/L was 65%.

LDL-C and non-HDL-C goal achievement by LMT regimen was somewhat difficult to

interpret due to the unadjusted nature of analyses and potential self-selection bias,

resulting from the choice of LMT regimen in clinical practice being influenced by

baseline lipid levels and other patient-level factors.


Mean LDL-C was 2.4 mmol/L with approximately 26% achieving LDL-C <1.8 mmol/L.

Mean non-HDL-C was 3.2 mmol/L with approximately 33% achieving non-HDL-C <2.6

mmol/L. A summary of mean LDL-C and non-HDL-C levels and lipid goal achievement

are presented in Supplemental table S7. Achievement of LDL-C and non-HDL-C goals

was highest for the T1DM with CKD subgroup and lowest for the CKD alone subgroup.

The T1DM with CKD subgroup receiving medium-intensity statins had the highest lipid

goal achievement: 52% for LDL-C <1.8 mmol/L and 69% for non-HDL-C <2.6 mmol/L.

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Discussion

The use of statins for reducing atherogenic lipid levels is recommended across all global

guidelines for the prevention of incident ASCVD events. Recent guidelines have shifted

towards an approach of consistent and immediate initiation of the appropriate statin

intensity regimen for a particular indication regardless of baseline lipid levels. In

contrast, the standard approach has been to lower LDL-C (or non-HDL-C) below

defined thresholds. Our study, representing a UK general-practice population at high

risk for ASCVD events, provides several insights regarding the state of concordance of

2014 clinical practice with the updated NICE 2014 guidelines,7 which focus on the

intensity of the statin regimen. As a comparison, we also report on concordance with the

ESC/EAS 2011 guidelines,8 which focus on treatment to defined LDL-C goals.

We observed that 79% of individuals with ASCVD were receiving statin treatment,

with 6% being prescribed a regimen already concordant with the NICE 2014 guidelines

(atorvastatin 80 mg or equivalent). For the non-ASCVD group, we observed that 62%

were receiving statin treatment, with 15% being prescribed a regimen already

concordant with the NICE 2014 guidelines (at least atorvastatin 20 mg or equivalent).

Extrapolation of these findings to the UK population indicated that, out of 3.3 million

individuals with ASCVD, 2.4 million would require up-titration of statin therapy and 680

000 would require statin initiation (31% de-novo initiation, 60% re-initiation, and 9%

addition to non-statin LMT) to have full population-level concordance with these

recommendations. Of the 3.5 million individuals with high-risk non-ASCVD (i.e. fulfilling

DM- and/or CKD-based guideline criteria), 1.6 million would require up-titration of statin

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therapy and 1.4 million would require statin initiation (59% de-novo initiation, 36% re-

initiation, and 5% addition to non-statin LMT).

Our findings highlight a considerable gap between 2014 UK clinical practice and

achievement of full concordance with the NICE 2014 guideline recommendations.

Optimizing the implementation of the guidelines represents best practice and would

result in a reduction in ASCVD event risk. The practical impact on patients, and in

particular GPs, however, merits consideration. Firstly, for patients who are well-

established on a treatment regimen, changes in therapy can lead to reduced

compliance, greater reporting of adverse events, and additional time within the

healthcare system to monitor the changes in therapy. Secondly, in an environment

where primary care is already stretched, the impact of counselling 90% of eligible

patients for statin regimen changes is likely to be considerable both on time and

resources available in primary care without, for instance, an increase in the number of

GPs. Finally, as cholesterol targets no longer appear in the updated 2014/15 Quality

Outcomes Framework (QOF) in UK for rewarding the provision of quality of care by

GPs,15 and with QOF lacking mention of statin intensity, it is unclear how narrowing of

the gap between guidelines and clinical practice might be effectively incentivised.

As mentioned earlier, an alternative approach to atherogenic lipid management is to

aim for lipid goal achievement as recommended in the ESC/EAS guidelines. For the

ASCVD population, we observed that achievement of LDL-C <1.8 mmol/L and non-

HDL-C <2.6 mmol/L8 was only 31% and 42% overall; 38% and 52% for those on

medium-intensity statins; and 37% and 48% for those on high-intensity statins.

Comparatively lower goal achievement for those on high-intensity statin likely reflected

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the unadjusted nature of analysis, with patients on high-intensity statins likely starting

with higher baseline lipid levels. For the non-ASCVD population considered in the

analysis (i.e. fulfilling DM- and/or CKD-based guideline criteria), the ESC/EAS

guidelines recommend the same thresholds of <1.8 mmol/L and <2.6 mmol/L for LDL-C

and non-HDL-C, respectively.8 We observed achievement of these goals in only 26%

and 33% of the non-ASCVD patients; 40% and 49% for those on medium-intensity

statin; and 36% and 42% for those on high-intensity statin.

For those not on any statin, treatment with a medium-intensity statin is expected to

lower LDL-C by 35%, while for those on medium-intensity statin, increasing the dose to

high-intensity is expected to lower LDL-C by an incremental 15%.7 Given that average

LDL-C levels for those not on a statin in both ASCVD and non-ASCVD cohorts was

approximately 3.0 mmol/L, and for those on medium-intensity statins in both ASCVD

and non-ASCVD cohorts was approximately 2.0 mmol/L, it is unlikely that an average

LDL-C of <1.8 mmol/L can be achieved in these populations even by maximizing statin

treatment. From the perspective of a treat to LDL-C goal approach, our results suggest

an expanded role for evidence-based add-on therapies for LDL-C lowering, primarily

ezetimibe based on available data from the IMPROVE-IT trial in 2014.16

Prior reports from a generalisable UK population describing LMT utilisation and lipid

attainment in ASCVD and non-ASCVD cohorts are limited. Our study provides novel

data on how these populations are treated and how effective the treatment has been.

The recent EUROASPIRE IV study, representing the 2012-2013 time period, was

conducted in patients with a history of hospitalisation due to a coronary event with an

assessment date of 6 months to 3 years post event.17 The study reported LDL-C <1.8

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mmol/L achievement as only 19%. To our knowledge, the most recent study that

reported statin use in a generalisable UK population at high CV risk found statin use in

2007 as 72% for patients with a history of MI or coronary revascularisation and 36%

those with a history of angina but not MI.18 Statin use in the UK in those with ASCVD

without coronary conditions (e.g. ischaemic stroke or PAD) appears to be even further

under-reported. From 1995-2005, in individuals aged ≥50 years with a history of stroke

(not limited to ischaemic stroke), 32% of men and 26% of women were receiving

treatment with LMT.19 Data on statin use in individuals with DM or CKD without ASCVD

also do not appear to be well-reported. During 2006-2008, a diabetes registry

representing GPs in Scotland found 68% individuals with DM without ASCVD were

prescribed a statin.20 When compared to these data, our study suggests statin use has

increased in the UK. This increase is likely due to a multitude of influences, including

the NICE 2008 guidelines,21 landmark trials such as SPARCL which demonstrated the

benefits of statins in the post-ischaemic stroke population,22 and incorporation of statins

and lipid monitoring as quality measures in major pay-for-performance initiatives in the

UK.23

The continued recommendation for statin therapy for the ASCVD population from

both the 2008 to the 2014 NICE guidelines 7,21 suggest that the 21% rate of statin non-

use in this population is largely due to discontinuation, a hypothesis that is supported by

our findings which indicate that approximately 60% of statin non-use in the ASCVD

population can be attributed to discontinuation (hence overall 13% [=21%*60%] of statin

non-use in ASCVD population is estimated to be due to discontinuation). High rates of

statin discontinuation have been documented in the literature. For example, in a UK

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primary-care database analysis representing the 1997–2006 time period, 20% of

patients initiated on a statin after an MI discontinued therapy at 1 year.24 For the non-

ASCVD population, the higher observed rate of statin non-use (38%) likely reflects not

only statin discontinuation but many patients who have never been prescribed LMT. Our

study suggests that approximately 59% of statin non-use in the non-ASCVD population

can be attributed to non-initiation of LMT therapy. Prior to the 2014 NICE guidelines,

some of these patients may not have qualified for LMT due to higher risk thresholds in

the NICE 2008 guidelines and the absence of certain conditions such as CKD as a

stand-alone criterion for statin therapy.7,21

Limitations

Availability of demographic and clinical characteristics was limited to information

available in the GP database. Certain data such as body-mass index, ethnicity, blood

pressure, and smoking status were not available for all patients. Lipid measurements

were not prospectively specified and the study cohort represents individuals with an

available lipid profile measurement, introducing the possibility of bias in findings. The

definition of LMT utilisation at the time of lipid measurements was optimised to provide

valid “on-treatment” measures, but ensuring whether patients fully took their prescribed

medications was not feasible from the database.

For consistency we based LMT categorization on the statin type and dose,

regardless of concomitant non-statin medications. This meant, for example, atorvastatin

10 mg + ezetimibe was categorized under medium potency statin, even though its

overall lipid-lowering efficacy is close to atorvastatin 80 mg. NICE 2014 guidelines

specifically recommend atorvastatin 80 mg and atorvastatin 20 mg, respectively, for the

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ASCVD and non-ASCVD populations considered in our study. During LMT

categorization, we included equivalent or higher potency statin therapy in order to

include situations where quality of care with lipid-lowering treatment was similar or

better. Of those treated with NICE 2014 guidelines according to our definition, 92%

received atorvastatin 80 mg in the ASCVD population, and 44% received atorvastatin

20 mg in the non-ASCVD population. Lower doses of atorvastatin are allowed by the

guidelines in case of potential drug interactions, high-risk of adverse effects, and patient

preference; but estimation of how frequently these cases occur was not feasible. In

individuals ≥85 years of age, NICE 2014 guidelines recommend a careful consideration

of patient-level factors informing the risk-benefit of statin treatment and intensity. Among

those not treated according to NICE 2014 guidelines in our study, approximately 14%

and 10% individuals within the ASCVD and non-ASCVD populations, respectively, were

≥85 years of age.

Our study was focused on the secondary prevention and high-risk primary

prevention populations; it did not include those for whom treatment would be

recommended for treatment based solely on a QRISK2 10-year risk of ≥10%. Thus the

analysis does not assess the full impact of the guidelines across all indications.

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Conclusions

In the UK, although 79% and 62% of ASCVD and high-risk non-ASCVD patients

respectively, received treatment with statin therapy in 2014, there existed a large gap in

terms of treatment concordance with the NICE 2014 guidelines recommendations

released during the same year, with up to 90% of both populations requiring

modification to their existing therapy. Extrapolating these results to the UK population,

up to 3 million ASCVD and 3 million high-risk non-ASCVD individuals (i.e. fulfilling DM-

and/or CKD-based guideline criteria) might require either statin up-titration or initiation in

order to attain full concordance with NICE 2014 guidelines. Achievement of ESC/EAS

2011 guideline criteria would also require statin up-titration, as approximately two-thirds

of individuals receiving moderate- or high-intensity statins were not at the recommended

LDL-C goal.

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Contributors

Dylan Steen was involved with the design of the study, interpretation of data, and critical

review of drafts.

Irfan Khan was involved with the design of the study, interpretation of data, and critical

review of drafts.

David Ansell was involved with the design of the study, acquisition, analysis, and

interpretation of data, and critical review of drafts.

Robert J. Sanchez was involved with the design of the study, interpretation of data, and


Kausik K. Ray was involved with the design of the study, interpretation of data, and


All authors provided final approval of the submitted manuscript.

Medical writing support was provided by Jeff Alexander from SNELL Medical

Communication, supported by Sanofi and Regeneron. Editorial assistance for later

drafts was provided by Neil Venn from Prime Medica, supported by Sanofi and

Regeneron.

Funding

This study was funded by Sanofi and Regeneron.

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Competing interests

Dylan Steen receives modest consulting fees from Sanofi and Regeneron. Irfan Khan is

a stockholder and employee of Sanofi. David Ansell is an employee of IMS Health.

Robert Sanchez is a stockholder and employee of Regeneron Pharmaceuticals, Inc.

Kausik Ray has received honoraria for advisory boards, lectures, or for serving on the

steering committee for clinical trials from Amgen, Sanofi, Regeneron, Pfizer,

AstraZeneca, Aegerion, Kowa, ISIS Pharma, MedCo, Cerenis, and Resverlogix, and

has received research support by grants to his institution from Pfizer, MSD, Amgen,

Sanofi, and Regeneron.

Ethics approval

This study was approved by the Scientific Review Committee, an independent UK-

based ethics committee established to review studies from The Health Improvement

Network (THIN).

Data sharing statement

The original analytic dataset is available on request by emailing the corresponding

author: [email protected].

Transparency

Dr Steen, as the lead author (the manuscript's guarantor) affirms that the manuscript is

an honest, accurate, and transparent account of the study being reported; no important

aspects of the study have been omitted and any discrepancies from the study as

planned have been explained.

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Copyright Statement

The Corresponding Author has the right to grant on behalf of all authors and does grant

on behalf of all authors, a worldwide licence to the Publishers and its licensees in

perpetuity, in all forms, formats and media (whether known now or created in the

future), to i) publish, reproduce, distribute, display and store the Contribution, ii)

translate the Contribution into other languages, create adaptations, reprints, include

within collections and create summaries, extracts and/or, abstracts of the Contribution,

iii) create any other derivative work(s) based on the Contribution, iv) to exploit all

subsidiary rights in the Contribution, v) the inclusion of electronic links from the

Contribution to third party material where-ever it may be located; and, vi) licence any

third party to do any or all of the above.

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References

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country.xls?ua=1. Accessed on January 14, 2016.

2. Institution for Health Metrics and Evaluation. Global burden of disease calculator:

United Kingdom, 2013. Available at: http://vizhub.healthdata.org/gbd-compare.

Accessed on January 14, 2016.

3. Cholesterol Treatment Trialists’ (CTT) Collaborators; Mihaylova B, Voysey M,

Gray A, et al. The effects of lowering LDL cholesterol with statin therapy in

people at low risk of vascular disease: Meta-analysis of individual data from 27

randomised trials. Lancet. 2012;380(9841):581-590.

4. CTT Collaborators; Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety

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HM. Risks associated with statin therapy: a systematic overview of randomised

clinical trials. Circulation. 2006;114(25):2788-2797.

6. Halcox JP, Tubach F, Lopez-Garcia E, et al. Low rates of both lipid-lowering

therapy use and achievement of low-density lipoprotein cholesterol targets in

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individuals at high-risk for cardiovascular disease across Europe. PLoS One.

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17. Kotseva K, Wood D, De Bacquer D, et al; on behalf of the EUROASPIRE

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atorvastatin after stroke or transient ischemic attack. N Engl J Med.

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Figure legends


Blue bars representing scenarios A and B (medication supply via recorded prescription [Rx] on or within 30 days prior

to the index date) define the patient as being treated as of the index date. The red bar representing scenario C

(medication supply via recorded Rx more than 30 days prior to the index date) defines the patient as not being

treated as of the index date.


*ASCVD includes acute coronary syndrome, other coronary heart disease, ischaemic stroke/transient ischaemic

attack, and peripheral arterial disease.

†Includes type 2 diabetes mellitus with QRISK2 ≥10%, type 1 diabetes mellitus with age >40 years, and chronic

kidney disease not meeting the previous diabetes mellitus criteria.

ASCVD=atherosclerotic cardiovascular disease; THIN=The Health Improvement Network

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Table 1. Baseline characteristics for the overall ASCVD and non-ASCVD cohorts and subgroups


Recent ACS (n=3112, 3%)

Other CHD (n=58 348,

64%)

Ischaemic stroke / TIA (n=19 785,

22%)

PAD (n=10 234,

11%)


T2DM with CKD

(n=11 102, 12%)

T2DM without CKD

(n=52 556, 57%)

T1DM with CKD

(n=749, 1%)

T1DM without CKD

(n=4204, 5%)

CKD alone (n=23 475,

25%)

Total non-ASCVD

(n=92 086)


Age, mean, years (SD) 67.8 (12.8) 72.8 (10.5) 73.0 (11.8) 72.3 (10.6) 72.6 (10.9) 75.7 (9.2) 67.2 (10.3) 69.7 (12.0) 57.2 (11.1) 74.6 (10.6) 69.7 (11.3)

Male, % 66.5 63.5 50.3 62.8 60.7 41.3 58.6 40.7 57.6 35.0 50.3

SDI*, mean (SD) 2.7 (1.4) 2.7 (1.4) 2.6 (1.4) 2.8 (1.4) 2.7 (1.4) 2.7 (1.4) 2.8 (1.4) 2.7 (1.5) 2.6 (1.4) 2.6 (1.4) 2.7 (1.4)

Ethnicity, %

White 28.3 30.3 29.1 30.0 30.0 29.0 29.4 25.1 30.0 27.9 28.9

South Asian† 1.9 1.5 1.1 0.7 1.4 2.0 4.1 1.5 1.6 1.0 2.9

Black Caribbean / African 0.3 0.3 0.6 0.4 0.3 1.2 1.1 1.6 1.3 0.7 1.0

Chinese / other East Asian 13.2 12.6 12.9 12.3 12.6 13.8 12.9 13.4 13.7 14.5 13.4

Not recorded 56.4 55.4 56.4 56.6 55.8 54.0 52.5 58.5 53.3 55.9 53.7

Current smoker, % 15.2 12.1 13.5 26.6 14.1 7.0 14.9 10.8 16.3 7.1 11.9

BMI, mean, kg/m2 (SD) 28.4 (5.4) 28.6 (5.3) 27.8 (5.5) 27.6 (5.4) 28.3 (5.4) 30.4 (6.2) 30.9 (6.3) 29.8 (6.3) 28.3 (5.8) 28.3 (5.5) 30.1 (6.2)

Systolic BP, mean (SD) 128.9 (17.8) 131.5 (15.7) 133.1 (15.8) 134.6 (16.3) 132.1 (15.9) 134.5 (15.0) 134.7 (14.1) 134.7 (16.2) 131.1 (14.8) 134.1 (15.8) 134.3 (14.8)


Recent ACS, % 100.0 0.0 0.0 0.0 3.4 N/A N/A N/A N/A N/A N/A

Other CHD, % 64.2 100.0 0.0 0.0 66.0 N/A N/A N/A N/A N/A N/A

Ischaemic stroke/TIA, % 7.6 10.5 100.0 0.0 28.6 N/A N/A N/A N/A N/A N/A

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PAD, % 10.1 11.2 14.0 100.0 21.7 N/A N/A N/A N/A N/A N/A

DM, % 27.0 30.1 25.6 33.7 29.4 100.0 100.0 100.0 100.0 7.1 76.3

Hypertension, % 50.4 61.5 62.1 64.2 61.5 77.4 62.2 74.4 41.8 73.2 66.0

History of CHF, % 14.0 11.2 4.2 5.1 9.1 1.4 0.5 6.9 1.0 7.1 2.4

CKD, stage III, % 17.2 24.4 22.1 23.0 23.5 100.0 0.0 100.0 0.0 100.0 38.2

CKD, stage IV-V, %‡ 0.2 0.3 0.2 0.3 0.2 1.2 0.0 2.0 0.0 0.8 0.3


Beta-blockers, % 81.4 60.1 23.5 22.4 48.7 N/A N/A N/A N/A N/A N/A

ACEI/ARBs, % 85 65.3 52.1 52.4 61.7 74.6 59.3 77.8 52.7 59.9 61.1

Antiplatelets,# % 52.5 13.5 29.7 15.4 18.5 N/A N/A N/A N/A N/A N/A

*Social deprivation index (SDI) as defined by the Townsend deprivation index score analysed in quintiles, 1 = most affluent and 5 = least affluent

†Includes Indian, Pakistani, Bangladeshi, and other South Asian individuals

‡Stage V CKD includes end-stage renal disease and dialysis

¶Medication use on index date

#Clopidogrel/ticagrelor/prasugrel



ACEI=angiotensin converting enzyme inhibitor; ACS=acute coronary syndrome; ARB=angiotensin II receptor blocker; ASCVD=atherosclerotic cardiovascular disease; BMI=body-mass index; BP=blood pressure;

CHD=coronary heart disease; CHF=congestive heart failure; CKD=chronic kidney disease; DM=diabetes mellitus; N/A=not applicable; PAD=peripheral arterial disease; SD=standard deviation; SDI=Social deprivation

index; T1DM=type 1 diabetes mellitus; T2DM=type 2 diabetes mellitus; TIA=transient ischaemic attack

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Table 2. Use of LMT in the overall ASCVD and non-ASCVD cohorts and subgroups


Recent ACS (n=3112)



PAD (n=10 234)


T2DM with CKD

(n=11 102)

T2DM without CKD

(n=52 556)

T1DM with CKD

(n=749)

T1DM without CKD

(n=4204)


Total non-ASCVD

(n=92 086)

High-intensity statin, % 62.4 34.6 21.5 23.2 31.4 20.0 18.6 29.0 21.1 11.1% 17.0

Monotherapy, % 93.3 91.8 93.2 92.3 92.2 91.1 93.5 92.6 90.2 93.3 93.0

Plus ezetimibe, % 1.0 4.8 2.9 3.4 4.1 3.2 2.4 4.1 5.1 2.7 2.8

Plus other non-statin LMT, % 5.8 3.4 3.9 4.3 3.7 5.7 4.0 3.2 4.7 4.0 4.3

Medium-intensity statin, % 22.6 41.4 46.2 44.3 42.1 44.7 43.0 39.5 36.5 33.1 40.4

Monotherapy, % 98.6 97.9 98.7 98.6 98.2 97.9 98.4 96.3 97.7 98.9 98.4

Plus ezetimibe, % 0.6 1.2 0.7 0.6 1.0 0.6 0.6 1.7 1.4 0.5 0.6


Low-intensity statin, % 2.1 5.9 5.5 5.1 5.6 6.4 4.9 4.9 4.4 4.8 5.0

Monotherapy, % 93.8 95.9 97.4 97.1 96.3 96.2 98.1 89.2 95.6 98.3 97.7

Plus ezetimibe, % 6.3 3.2 1.7 2.3 2.8 2.3 1.1 8.1 2.7 1.0 1.4


Non-statins only, % 0.9 2.0 1.7 1.9 1.9 2.5 1.6 3.9 2.0 1.7 1.8

Ezetimibe, % 70.4 61.3 65.5 55.6 61.6 47.9 54.2 58.6 61.6 45.5 51.5

Other non-statin LMT, % 29.6 38.7 34.5 44.4 38.4 52.1 45.8 41.4 38.4 54.5 48.5

Not currently treated by LMT, % 12.1 16.2 25.1 25.4 19.0 26.4 31.9 22.7 35.9 49.4 35.8


20.7 16.4 8.6 9.3 13.2 7.7 6.1 18.2 9.1 3.3 5.5

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22.8 40.9 37.9 33.0 38.4 33.2 27.5 30.6 29.9 17.7 24.7


5.6 10.0 6.9 6.8 8.5 7.3 4.9 10.0 4.4 3.9 4.7

Previously on non-statin LMT, % 4.8 7.2 4.8 3.6 5.9 6.1 3.5 5.3 3.8 2.4 3.4

No previous LMT, % 46.1 25.5 41.8 47.3 34.0 45.7 58.0 35.9 52.8 72.7 61.7

Numbers in the grey bars denote absolute percentages, and add up to 100% vertically. Numbers in the white bars are relative percentages of the absolute percentages in the grey bars. ASCVD subgroups represent

hierarchical categorisation. Non-ASCVD categorisations have been simplified by consideration of the qualifiers QRISK2 ≥10% and age >40 years as implicit in the definitions of T2DM and T1DM, respectively, with and

without CKD, and of the qualifiers without T2DM+QRISK2 ≥10% or T1DM+ age >40 as implicit in the definition of CKD alone.

ACS=acute coronary syndrome; ASCVD=atherosclerotic cardiovascular disease; CHD=coronary heart disease; CKD=chronic kidney disease; LMT=lipid modifying therapy; PAD=peripheral arterial disease; T1DM=type

1 diabetes mellitus; T2DM=type 2 diabetes mellitus; TIA=transient ischaemic attack

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Table 3. Statin treatment according to NICE guidelines in the overall ASCVD and non-ASCVD cohorts and subgroups


Recent ACS (n=3112)



PAD (n=10 234)


T2DM with CKD

(n=11 102)

T2DM without CKD

(n=52 556)

T1DM with CKD

(n=749)

T1DM without CKD

(n=4204)


Total non-ASCVD

(n=92 086)

Study cohort, % (N)

Treated with statins of potency as per NICE guidelines*

33.1 (1029)

6.7 (3934)

2.0 (400)

2.2 (221)

6.1 (5584)

18.6 (2065)

17.2 (9038)

26.2 (196)

19.3 (812)

10.3 (2421)

15.8 (14 532)

Treated with statins of lower potency*

54.0 (1679)

75.1 (43 802)

71.2 (14 079)

70.5 (7216)

73.0 (66 776)

52.5 (5825)

49.3 (25 913)

47.3 (354)

42.7 (1796)

38.6 (9062)

46.6 (42 950)

Treated with only non-statin LMT 0.9 (27)

2.0 (1188)

1.7 (339)

1.9 (196)

1.9 (1750)

2.5 (282)

1.6 (858)

3.9 (29)

2.0 (86)

1.7 (402)

1.8 (1657)

Not treated by LMT 12.1 (377)

16.2 (9424)

25.1 (4967)

25.4 (2601)

19.0 (17 369)

26.4 (2930)

31.9 (16 747)

22.7 (170)

35.9 (1510)

49.4 (11 590)

35.8 (32 947)

Adjusted extrapolation to the UK population, N

Treated with statins of potency as per NICE guidelines*

34 085 147 215 15 653 4869 201 822 112 119 209 589 10 642 18 830 156 621 507 801

Treated with statins of lower potency*

55 615 1 639 122 550 930 158 966 2 404 633 316 269 600 916 19 220 41 649 586 243 1 564 297

Treated with only non-statin LMT 894 44 456 13 266 4318 62 934 15 311 19 897 1575 1994 26 006 64 783

Not treated by LMT 12 488 352 657 194 365 57 299 616 809 159 085 388 359 9230 35 017 749 786 1 341 477

*NICE 2014 guidelines recommend atorvastatin 80 mg and 20 mg, respectively, for the ASCVD and non-ASCVD populations in the table. We have included statins of equivalent or higher potency with ASCVD definition

based on atorvastatin 80 mg, rosuvastatin 40 mg, and non-ASCVD definition based on atorvastatin 20, 40 and 80 mg, rosuvastatin 10, 20 and 40 mg, and simvastatin 80 mg. It should be noted that NICE guidelines

allow for consideration of a lower dose based on clinical considerations and patient preference.



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ACS=acute coronary syndrome; ASCVD=atherosclerotic cardiovascular disease; CHD=coronary heart disease; CKD=chronic kidney disease; LMT=lipid modifying therapy; NICE=National Institute for Health and Care

Excellence; PAD=peripheral arterial disease; T1DM=type 1 diabetes mellitus; T2DM=type 2 diabetes mellitus; TIA=transient ischaemic attack; UK=United Kingdom

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122x47mm (300 x 300 DPI)

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121x87mm (300 x 300 DPI)

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Supplementary Appendix

Methodology for adjusted extrapolation to the United Kingdom (UK) population

Findings on the number of patients treated according to National Institute for Health and

Care Excellence (NICE) 2014 guidelines were extrapolated to the UK population via the

following methodology that accounted for adjustments by patient demographic and

clinical profiles. The study cohort was initially divided into mutually exclusive strata

based on status representing presence of coronary heart disease (CHD; including

recent acute coronary syndrome [ACS] and other CHD), ischaemic stroke / transient

ischaemic attack (TIA), peripheral arterial disease (PAD), diabetes mellitus (DM),

chronic kidney disease (CKD), dichotomous age groups (20–70 years versus ≥70

years), and gender. An example of strata would be a profile representing male, aged

≥70 years, with CHD and DM. Differential weights by these mutually exclusive strata

were then estimated via an optimisation algorithm to minimise the difference between

estimated totals for aggregate categories (not mutually exclusive) representing CHD,

ischaemic stroke/TIA, PAD, DM, CKD, age groups, and gender, and their reported

prevalence in the UK based on published sources. The estimated weights by strata

were then utilised to scale the results. The methodology helped ensure the extrapolation

accounted for differential scaling by patient profiles and eliminated double counting due

to overlap between conditions. Estimation of weights via optimisation methodology was

conducted using Excel Solver.

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Methodology for estimation of QRISK2 10-year risk

The QRISK2 10-year risk was estimated only for the non-ASCVD T2DM population in

our study. It was estimated as: Risk = 1 − S0exp(∑βiXi), with S0 and βi obtained from the

QResearch® group at https://github.com/robdyke/clinrisk-qRisk2/tree/master/QRISK2-

2015-lgpl-source. The calculation was validated by comparing the calculated result for

50 random patients with the online version of the QRISK2 risk calculator, available at:

https://qrisk.org/2016. In case a variable (e.g. BP) was not available as of the index

date, an older value was searched and the most recent data was utilised. In case the

value for a particular variable was completely missing, the calculation was conducted

without adding the corresponding 𝛽𝑖𝑋𝑖 term, which effectively meant an incremental

regression of the 10-year risk estimate towards S0, denoting an approximately 1% 10-

year risk. In other words, any missing data resulted in a calculation that made it more

likely that a patient would not qualify under 10-year risk ≥10% criterion. Approximately

20% of the non-ASCVD T2DM population had at least one missing variable for the

estimation of QRISK2 10-year risk, with more than 90% of these instances representing

missing data on the social deprivation index.

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https://github.com/robdyke/clinrisk-qRisk2/tree/master/QRISK2-2015-lgpl-source

https://github.com/robdyke/clinrisk-qRisk2/tree/master/QRISK2-2015-lgpl-source

https://qrisk.org/2016


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SUPPLEMENTAL TABLE S1. Standardised Diagnostic Read Codes Used to Define

Patient Cohorts

ASCVD

ACS

G30..00 ACUTE MYOCARDIAL INFARCTION

G30..11 ATTACK - HEART

G30..12 Coronary thrombosis

G30..13 CARDIAC RUPTURE FOLLOWING MYOCARDIAL INFARCTION (MI)

G30..14 HEART ATTACK

G30..15 MI - ACUTE MYOCARDIAL INFARCTION

G30..16 Thrombosis - coronary

G300.00 ACUTE ANTEROLATERAL INFARCTION

G301.00 OTHER SPECIFIED ANTERIOR MYOCARDIAL INFARCTION

G301000 ACUTE ANTEROAPICAL INFARCTION

G301100 ACUTE ANTEROSEPTAL INFARCTION

G301z00 ANTERIOR MYOCARDIAL INFARCTION NOS

G302.00 ACUTE INFEROLATERAL INFARCTION

G303.00 ACUTE INFEROPOSTERIOR INFARCTION

G304.00 POSTERIOR MYOCARDIAL INFARCTION NOS

G305.00 LATERAL MYOCARDIAL INFARCTION NOS

G306.00 TRUE POSTERIOR MYOCARDIAL INFARCTION

G307.00 ACUTE SUBENDOCARDIAL INFARCTION

G307000 ACUTE NON-Q WAVE INFARCTION

G307100 ACUTE NON-ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

G308.00 INFERIOR MYOCARDIAL INFARCTION NOS

G309.00 ACUTE Q-WAVE INFARCT

G30B.00 ACUTE POSTEROLATERAL MYOCARDIAL INFARCTION

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G30X.00 ACUTE TRANSMURAL MYOCARDIAL INFARCTION OF UNSPECIFIED SITE

G30X000 ACUTE ST SEGMENT ELEVATION MYOCARDIAL INFARCTION

G30y.00 OTHER ACUTE MYOCARDIAL INFARCTION

G30y000 ACUTE ATRIAL INFARCTION

G30y100 ACUTE PAPILLARY MUSCLE INFARCTION

G30y200 ACUTE SEPTAL INFARCTION

G30yz00 OTHER ACUTE MYOCARDIAL INFARCTION NOS

G30z.00 ACUTE MYOCARDIAL INFARCTION NOS

G31..00 Other acute and subacute ischaemic heart disease

G310.00 Postmyocardial infarction syndrome

G310.11 Dressler’s syndrome

G311500 Acute coronary syndrome

G312.00 Coronary thrombosis not resulting in myocardial infarction

G31y.00 Other acute and subacute ischaemic heart disease

G31y000 Acute coronary insufficiency

G31y100 MICROINFARCTION OF HEART

G31y200 Subendocardial ischaemia

G31y300 Transient myocardial ischaemia

G31yz00 Other acute and subacute ischaemic heart disease NOS

G35..00 Subsequent myocardial infarction

G350.00 Subsequent myocardial infarction of anterior wall

G351.00 Subsequent myocardial infarction of inferior wall

G353.00 Subsequent myocardial infarction of other sites

G35X.00 Subsequent myocardial infarction of unspecified site

G36..00 Certain current complication follow acute myocardial infarct

G360.00 Haemopericardium/current comp following acute myocardial infarction

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G361.00 Atrial septal defect/current comp following acute myocardial infarction

G362.00 Ventric septal defect/current comp following acute myocardial infarction

G363.00 Rupture of cardiac wall without haemopericard/current comp following acute myocardial infarction

G364.00 Ruptur chordae tendinae/current comp following acute myocardial infarction

G365.00 Rupture papillary muscle/current comp following acute myocardial infarction

G366.00 Thrombosis atrium,auric appendvent/current comp following acute myocardial infarction

G38..00 Postoperative myocardial infarction

G380.00 Postoperative transmural myocardial infarction anterior wall

G381.00 Postoperative transmural myocardial infarction inferior wall

G382.00 Postoperative transmural myocardial infarction other sites

G383.00 Postoperative transmural myocardial infarction unspecified site

G384.00 Postoperative subendocardial myocardial infarction

G38z.00 Postoperative myocardial infarction, unspecified

Gyu3400 [X]ACUTE TRANSMURAL MYOCARDIAL INFARCTION OF UNSPECIFIED SITE

Gyu3500 [X]Subsequent myocardial infarction of other sites

Gyu3600 [X]Subsequent myocardial infarction of unspecified site

G311.00 Preinfarction syndrome

G311.11 Crescendo angina

G311.12 Impending infarction

G311.13 Unstable angina

G311.14 Angina at rest

G311000 Myocardial infarction aborted

G311011 MI - myocardial infarction aborted

G311100 Unstable angina

G311200 Angina at rest

G311300 Refractory angina

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G311400 Worsening angina

G311z00 Preinfarction syndrome NOS

G330.00 Angina decubitus

G330000 Nocturnal angina

G330z00 Angina decubitus NOS

G33z500 Post infarct angina

G33z600 New onset angina

Other CHD

792E000 Emergency percutaneous coronary intervention

7920.00 SAPHENOUS VEIN GRAFT REPLACEMENT OF CORONARY ARTERY

7920.11 SAPHENOUS VEIN GRAFT BYPASS OF CORONARY ARTERY

7921.00 OTHER AUTOGRAFT REPLACEMENT OF CORONARY ARTERY

7921.11 OTHER AUTOGRAFT BYPASS OF CORONARY ARTERY

7922.00 ALLOGRAFT REPLACEMENT OF CORONARY ARTERY

7922.11 ALLOGRAFT BYPASS OF CORONARY ARTERY

7923.00 PROSTHETIC REPLACEMENT OF CORONARY ARTERY

7923.11 PROSTHETIC BYPASS OF CORONARY ARTERY

7924.00 REVISION OF BYPASS FOR CORONARY ARTERY

7925.00 CONNECTION OF MAMMARY ARTERY TO CORONARY ARTERY

7925.11 CREATION OF BYPASS FROM MAMMARY ARTERY TO CORONARY ARTERY

7926.00 CONNECTION OF OTHER THORACIC ARTERY TO CORONARY ARTERY

7927.00 OTHER OPEN OPERATIONS ON CORONARY ARTERY

7928.00 TRANSLUMINAL BALLOON ANGIOPLASTY OF CORONARY ARTERY

7928.11 PERCUTANEOUS BALLOON CORONARY ANGIOPLASTY

7929.00 OTHER THERAPEUTIC TRANSLUMINAL OPERATIONS ON CORONARY ARTERY

7920000 SAPHENOUS VEIN GRAFT REPLACEMENT OF ONE CORONARY ARTERY

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7920100 SAPHENOUS VEIN GRAFT REPLACEMENT OF TWO CORONARY ARTERIES

7920200 SAPHENOUS VEIN GRAFT REPLACEMENT OF THREE CORONARY ARTERIES

7920300 SAPHENOUS VEIN GRAFT REPLACEMENT OF FOUR+ CORONARY ARTERIES

7921000 AUTOGRAFT REPLACEMENT OF ONE CORONARY ARTERY NEC

7921100 AUTOGRAFT REPLACEMENT OF TWO CORONARY ARTERIES NEC

7921200 AUTOGRAFT REPLACEMENT OF THREE CORONARY ARTERIES NEC

7921300 AUTOGRAFT REPLACEMENT OF FOUR OF MORE CORONARY ARTERIES NEC

7922000 ALLOGRAFT REPLACEMENT OF ONE CORONARY ARTERY

7922100 ALLOGRAFT REPLACEMENT OF TWO CORONARY ARTERIES

7922200 ALLOGRAFT REPLACEMENT OF THREE CORONARY ARTERIES

7922300 ALLOGRAFT REPLACEMENT OF FOUR+ CORONARY ARTERIES

7923000 PROSTHETIC REPLACEMENT OF ONE CORONARY ARTERY

7923100 PROSTHETIC REPLACEMENT OF TWO CORONARY ARTERIES

7923200 PROSTHETIC REPLACEMENT OF THREE CORONARY ARTERIES

7923300 PROSTHETIC REPLACEMENT OF FOUR+ CORONARY ARTERIES

7924000 REVISION OF BYPASS FOR ONE CORONARY ARTERY

7924100 REVISION OF BYPASS FOR TWO CORONARY ARTERIES

7924200 REVISION OF BYPASS FOR THREE CORONARY ARTERIES

7924300 REVISION OF BYPASS FOR FOUR+ CORONARY ARTERIES

7924400 REVISION OF CONNECTION OF THORACIC ARTERY TO CORONARY ARTERY

7924500 REVISION OF IMPLANTATION OF THORACIC ARTERY INTO HEART

7925000 DOUBLE ANASTOMOSIS OF MAMMARY ARTERIES TO CORONARY ARTERIES

7925011 LIMA sequential anastomosis

7925012 RIMA sequential anastomosis

7925100 DOUBLE IMPLANT OF MAMMARY ARTERIES INTO CORONARY ARTERIES

7925200 SINGLE ANAST MAMMARY ART TO LEFT ANT DESCEND CORONARY ART

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7925300 SINGLE ANASTOMOSIS OF MAMMARY ARTERY TO CORONARY ARTERY NEC

7925311 LIMA single anastomosis

7925312 RIMA single anastomosis

7925400 SINGLE IMPLANTATION OF MAMMARY ARTERY INTO CORONARY ARTERY

7926000 DOUBLE ANASTOM THORACIC ARTERIES TO CORONARY ARTERIES NEC

7926100 DOUBLE IMPLANT THORACIC ARTERIES INTO CORONARY ARTERIES NEC

7926200 SINGLE ANASTOMOSIS OF THORACIC ARTERY TO CORONARY ARTERY NEC

7926300 SINGLE IMPLANTATION THORACIC ARTERY INTO CORONARY ARTERY NEC

7927500 OPEN ANGIOPLASTY OF CORONARY ARTERY

7928000 PERCUT TRANSLUMINAL BALLOON ANGIOPLASTY ONE CORONARY ARTERY

7928100 PERCUT TRANSLUM BALLOON ANGIOPLASTY MULT CORONARY ARTERIES

7928200 PERCUT TRANSLUM BALLOON ANGIOPLASTY BYPASS GRAFT CORONARY A

7928300 PERCUT TRANSLUM CUTTING BALLOON ANGIOPLASTY CORONARY ARTERY

7929000 PERCUTANEOUS TRANSLUMINAL LASER CORONARY ANGIOPLASTY

7929100 Percut transluminal coronary thrombolysis with streptokinase

7929111 Percut translum coronary thrombolytic therapy - streptokinase

7929200 PERCUTAN. TRANSLUM. INJECT THERAP SUBST TO CORONARY ARTERY NEC

7929200 Percut translum inject therap subst to coronary artery NEC

7929300 ROTARY BLADE CORONARY ANGIOPLASTY

7929400 INSERTION OF CORONARY ARTERY STENT

7929500 INSERTION OF DRUG-ELUTING CORONARY ARTERY STENT

7929600 PERCUTANEOUS TRANSLUMINAL ATHERECTOMY OF CORONARY ARTERY

790H300 Revascularisation of wall of heart

792..00 CORONARY ARTERY OPERATIONS

792..11 CORONARY ARTERY BYPASS GRAFT OPERATIONS

7920y00 SAPHENOUS VEIN GRAFT REPLACEMENT OF CORONARY ARTERY OS

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7920z00 SAPHENOUS VEIN GRAFT REPLACEMENT CORONARY ARTERY NOS

7921y00 OTHER AUTOGRAFT REPLACEMENT OF CORONARY ARTERY OS

7921z00 OTHER AUTOGRAFT REPLACEMENT OF CORONARY ARTERY NOS

7922y00 OTHER SPECIFIED ALLOGRAFT REPLACEMENT OF CORONARY ARTERY

7922z00 ALLOGRAFT REPLACEMENT OF CORONARY ARTERY NOS

7923y00 OTHER SPECIFIED PROSTHETIC REPLACEMENT OF CORONARY ARTERY

7923z00 PROSTHETIC REPLACEMENT OF CORONARY ARTERY NOS

7924y00 OTHER SPECIFIED REVISION OF BYPASS FOR CORONARY ARTERY

7924z00 REVISION OF BYPASS FOR CORONARY ARTERY NOS

7925y00 CONNECTION OF MAMMARY ARTERY TO CORONARY ARTERY OS

7925z00 CONNECTION OF MAMMARY ARTERY TO CORONARY ARTERY NOS

7926y00 CONNECTION OF OTHER THORACIC ARTERY TO CORONARY ARTERY OS

7926z00 CONNECTION OF OTHER THORACIC ARTERY TO CORONARY ARTERY NOS

7927y00 OTHER SPECIFIED OTHER OPEN OPERATION ON CORONARY ARTERY

7927z00 OTHER OPEN OPERATION ON CORONARY ARTERY NOS

7928y00 TRANSLUMINAL BALLOON ANGIOPLASTY OF CORONARY ARTERY OS

7928z00 TRANSLUMINAL BALLOON ANGIOPLASTY OF CORONARY ARTERY NOS

7929y00 OTHER THERAPEUTIC TRANSLUMINAL OP ON CORONARY ARTERY OS

7929z00 OTHER THERAPEUTIC TRANSLUMINAL OP ON CORONARY ARTERY NOS

792A.00 DIAGNOSTIC TRANSLUMINAL OPERATIONS ON CORONARY ARTERY

792B.00 REPAIR OF CORONARY ARTERY NEC

792B000 Endarterectomy of coronary artery NEC

792By00 Other specified repair of coronary artery

792Bz00 Repair of coronary artery NOS

792C.00 OTHER REPLACEMENT OF CORONARY ARTERY

792C000 REPLACEMENT OF CORONARY ARTERIES USING MULTIPLE METHODS

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792Cy00 OTHER SPECIFIED REPLACEMENT OF CORONARY ARTERY

792Cz00 REPLACEMENT OF CORONARY ARTERY NOS

792D.00 OTHER BYPASS OF CORONARY ARTERY

792Dy00 OTHER SPECIFIED OTHER BYPASS OF CORONARY ARTERY

792Dz00 OTHER BYPASS OF CORONARY ARTERY NOS

792E.00 Percutaneous coronary intervention

792y.00 OTHER SPECIFIED OPERATIONS ON CORONARY ARTERY

792z.00 Coronary artery operations NOS

793G.00 Perc translumin balloon angioplasty stenting coronary artery

793G000 Perc translum balloon angioplasty insert 1-2 drug elut stents cor art

793G100 Perc translum balloon angioplasty ins 3 or more drug elut stents cor art

793G200 Perc translum balloon angioplasty insert 1-2 stents cor art

793G300 Percutaneous cor balloon angioplasty 3 more stents cor art NEC

793Gy00 OS perc translum balloon angioplasty stenting coronary art

793Gz00 Perc translum balloon angioplasty stenting coronary art NOS

793K.00 Transluminal operations internal mammary artery side branch

793K000 Transluminal occlusion left internal mammary artery side branch

793Ky00 OS transluminal operations internal mammary art side branch

793Kz00 Transluminal operations internal mammary art side branch NOS

SP00300 MECHANICAL COMPLICATION OF CORONARY BYPASS

ZV45700 [V]Presence of aortocoronary bypass graft

3232.00 ECG: old myocardial infarction

14A3.00 H/O: myocardial infarct <60

14A4.00 H/O: myocardial infarct >60

14AH.00 H/O: Myocardial infarction in last year

14AT.00 History of myocardial infarction

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G30..17 Silent myocardial infarction

G32..00 Old myocardial infarction

G32..11 Healed myocardial infarction

G32..12 Personal history of myocardial infarction

G344.00 Silent myocardial ischaemia

8B3k.00 Coronary heart disease medication review

8CMP.00 Coronary heart disease care plan

8CR6.00 Coronary heart disease risk clinical management plan

8I37.00 Coronary heart disease monitoring refused

9Ob..00 Coronary heart disease monitoring administration

9Ob0.00 Attends coronary heart disease monitoring

9Ob1.00 Refuses coronary heart disease monitoring

9Ob2.00 Coronary heart disease monitoring default

9Ob3.00 Coronary heart disease monitoring 1st letter

9Ob4.00 Coronary heart disease monitoring 2nd letter

9Ob5.00 Coronary heart disease monitoring 3rd letter

9Ob6.00 Coronary heart disease monitoring verbal invitation

9Ob7.00 Coronary heart disease monitoring deleted

9Ob8.00 Coronary heart disease monitoring check done

9Ob9.00 Coronary heart disease monitoring telephone invite

G3...11 Arteriosclerotic heart disease

G3...12 Atherosclerotic heart disease

G34..00 Other chronic ischaemic heart disease

G340.00 Coronary atherosclerosis

G340.11 Triple vessel disease of the heart

G340.12 Coronary artery disease

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G340000 Single coronary vessel disease

G342.00 Atherosclerotic cardiovascular disease

G343.00 Ischaemic cardiomyopathy

G34y.00 Other specified chronic ischaemic heart disease

G34y000 Chronic coronary insufficiency

G34y100 Chronic myocardial ischaemia

G34yz00 Other specified chronic ischaemic heart disease NOS

G34z.00 Other chronic ischaemic heart disease NOS

G34z000 Asymptomatic coronary heart disease

G39..00 Coronary microvascular disease

3889.00 Euroscore for angina

14A5.00 H/O: angina pectoris

14AJ.00 H/O: angina in last year

187..00 Frequency of angina

388E.00 Canadian Cardiovascular Society classification of angina

388F.00 Cardiovascular Limitations and Symptoms Profile angina score

661M000 Angina self-management plan agreed

661N000 Angina self-management plan review

662K.00 Angina control

662K000 Angina control - good

662K100 Angina control - poor

662K200 Angina control - improving

662K300 Angina control - worsening

662Kz00 Angina control NOS

8B27.00 Antianginal therapy

8IEY.00 Referral to Angina Plan self-management programme declined

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8T04.00 Referral to Angina Plan self-management programme

G33..00 Angina pectoris

G331.11 Variant angina pectoris

G33z.00 Angina pectoris NOS

G33z000 Status anginosus

G33z100 Stenocardia

G33z200 Syncope anginosa

G33z300 Angina on effort

G33z400 Ischaemic chest pain

G33z700 Stable angina

G33zz00 Angina pectoris NOS

Gyu3000 [X]Other forms of angina pectoris

J421.11 Angina - abdominal

ZR37.00 Canadian Cardiovascular Society classification of angina



ZRB1.00 Euroscore for angina

Ischaemic stroke/TIA

G63..11 Infarction - precerebral

G632.00 Vertebral artery occlusion

G633.00 Multiple and bilateral precerebral arterial occlus

G63y000 Cerebral infarct due to thrombosis of precerebral arteries

G63y100 Cerebral infarction due to embolism of precerebral arteries

G64..00 Cerebral arterial occlusion

G64..11 CVA - cerebral artery occlusion

G64..12 Infarction - cerebral

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G64..13 Stroke due to cerebral arterial occlusion

G640.00 Cerebral thrombosis

G640000 Cerebral infarction due to thrombosis of cerebral

G64z.00 Cerebral infarction NOS

G64z.11 Brainstem infarction NOS

G64z.12 Cerebellar infarction

G64z000 Brainstem infarction

G64z100 Wallenberg syndrome

G64z200 Left sided cerebral infarction

G64z300 Right sided cerebral infarction

G64z400 Infarction of basal ganglia

G671000 Acute cerebrovascular insufficiency NOS

G677000 Occlusion and stenosis of middle cerebral artery

G677100 Occlusion and stenosis of anterior cerebral artery

G677200 Occlusion and stenosis of posterior cerebral arter

G677300 Occlusion and stenosis of cerebellar arteries

G677400 Occlusion and stenosis of multiple and bilat cerebral

G6W..00 Cereb infarct due unsp occlus/stenos precerebr art

G6W..00 Cereb infarct due unsp occlus/stenos precerebr arteries

G6X..00 Cereb infarct due/unspcf occlusn or sten/cerebr

G6X..00 Cereb infarct due/unspcf occlusn or sten/cerebrl artrs

Gyu6300 [X]Cereb infarct due/unspcf occlusn or sten/cerebrl artrs

Gyu6400 [X]Other cerebral infarction

Gyu6600 [X]Occlusion and stenosis of other cerebral arteries

Gyu6G00 [X]Cereb infarct due unsp occlus/stenos precerebr arteries

14AB.00 H/O: TIA

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1JK..00 Suspected transient ischaemic attack

8CRB.00 Transient ischaemic attack clinical management plan

8HBJ.00 Stroke / transient ischaemic attack referral

9Om..00 Stroke/transient ischaemic attack monitoring administration

9Om0.00 Stroke/transient ischaemic attack monitoring first letter

9Om1.00 Stroke/transient ischaemic attack monitoring second letter

9Om2.00 Stroke/transient ischaemic attack monitoring third letter

9Om3.00 Stroke/transient ischaemic attack monitoring verbal invitati

9Om4.00 Stroke/transient ischaemic attack monitoring telephone invte

F580200 Transient ischaemic deafness

ZV12D00 [V]Personal history of transient ischaemic attack

G65..00 Transient cerebral ischaemia

G65..11 Drop attack

G65..12 Transient ischaemic attack

G65..13 Vertebro-basilar insufficiency

G650.00 Basilar artery syndrome

G650.11 Insufficiency - basilar artery

G651.00 Vertebral artery syndrome

G651000 Vertebro-basilar artery syndrome

G652.00 Subclavian steal syndrome


G654.00 Multiple and bilateral precerebral artery syndromes

G655.00 Transient global amnesia

G656.00 Vertebrobasilar insufficiency

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G657.00 Carotid territory transient ischaemic attack

G65y.00 Other transient cerebral ischaemia

G65z.00 Transient cerebral ischaemia NOS

G65z000 Impending cerebral ischaemia

G65z100 Intermittent cerebral ischaemia

G65zz00 Transient cerebral ischaemia NOS

14AB000 H/O amaurosis fugax

F423300 Retinal microembolism

F423400 Hollenhorst plaque

F423500 Retinal partial arterial occlusion NOS

F423600 Amaurosis fugax

F423700 Retinal transient arterial occlusion NOS

PAD

66f3.00 Aortic aneurysm monitoring

68B5100 Aortic aneurysm screening abnormal

7A11.00 Replacement of aneurysmal bifurcation of aorta

7A11000 Emerg repl aneurysm bifurc aorta by anast aorta to fem art

7A11100 Replace aneurysm bifurc aorta by anast aorta to femoral art

7A11200 Emerg repl aneurysm bifurc aorta by anast aorta to iliac a

7A11211 Y graft of abdominal aortic aneurysm (emergency)

7A11300 Replace aneurysm bifurc aorta by anast aorta to iliac artery

7A11311 Y graft abdominal aortic aneurysm

7A11y00 Replacement of aneurysmal bifurcation of aorta OS

7A11z00 Replacement of aneurysmal bifurcation of aorta NOS

7A13.11 Emergency repair of aortic aneurysm

7A13400 Emerg replace aneurysm abdom aorta by anast aorta/aorta NEC

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7A13411 Tube graft abdominal aortic aneurysm (emergency)

7A14.11 Aortic aneurysm repair

7A14400 Replace aneurysm abdominal aorta by anast aorta to aorta NEC

7A14411 Tube graft of abdominal aortic aneurysm

7A1B000 Endovascular stenting infrarenal abdominal aortic aneurysm

7A1B100 Endovascular stenting of suprarenal aortic aneurysm

7A1B600 Endovascular stenting for aortic aneurysm of bifurcation NEC

7A1B800 Endovascul insert stent infrarenal abdominal aortic aneurysm

7A1B900 Endovascular insertion stent for suprarenal aortic aneurysm

7A1BA00 Endovascular insertion of stent for thoracic aortic aneurysm

7A1BC00 Endovas insert stent for aortic aneurysm of bifurcation NEC

7A1C000 Endovas ins stent graft for infrarenal abdom aortic aneurysm

7A1C100 Endovas insert of stent graft for suprarenal aortic aneurysm

7A1C200 Endov insertion of stent graft for thoracic aortic aneurysm

G71..00 Aortic aneurysm

G713.00 Abdominal aortic aneurysm which has ruptured

G713.11 Ruptured abdominal aortic aneurysm

G713000 Ruptured suprarenal aortic aneurysm

G714.00 Abdominal aortic aneurysm without mention of rupture

G714.11 AAA - Abdominal aortic aneurysm without mention of rupture

G714000 Juxtarenal aortic aneurysm

G714200 Infrarenal abdominal aortic aneurysm

G714300 Aneurysm of suprarenal aorta

G715.00 Ruptured aortic aneurysm NOS

G715000 Thoracoabdominal aortic aneurysm, ruptured

G716.00 Aortic aneurysm without mention of rupture NOS

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G716000 Thoracoabdominal aortic aneurysm, without mention of rupture

G718.00 Leaking abdominal aortic aneurysm

G71z.00 Aortic aneurysm NOS

Gyu7100 [X]Aortic aneurysm of unspecified site, ruptured

Gyu7200 [X]Aortic aneurysm of unspecified site, nonruptured

7A20000 Replacement of carotid artery using graft

7A20100 Intracranial bypass to carotid artery

7A20200 Bypass to carotid artery NEC

7A20300 Endarterectomy and patch repair of carotid artery

7A20311 Carotid endarterectomy and patch

7A20400 Endarterectomy of carotid artery NEC

7A20500 High-flow inter extrac intrac byp ext carot art mid cer art

7A20600 Byp carot art anastom superfic tempor artery middle cere art

7A20700 Intracranial bypass from carotid artery NEC

7A20y00 Other specified reconstruction of carotid artery

7A20z00 Reconstruction of carotid artery NOS

7A21.00 Other open operations on carotid artery

7A21000 Repair of carotid artery NEC

7A21100 Ligation of carotid artery

7A22.00 Transluminal operations on carotid artery

7A22000 Percutaneous transluminal angioplasty of carotid artery

7A22200 Endovascular repair of carotid artery

7A22300 Percutaneous transluminal insertion stent carotid artery

7A22y00 Other specified transluminal operation on carotid artery

7A22z00 Transluminal operation on carotid artery NOS

G630.00 Basilar artery occlusion

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G631.00 Carotid artery occlusion

G631.11 Stenosis, carotid artery

G631.12 Thrombosis, carotid artery

G634.00 Carotid artery stenosis

G63y.00 Other precerebral artery occlusion

G63z.00 Precerebral artery occlusion NOS


G670.00 Cerebral atherosclerosis

G670.11 Precerebral atherosclerosis

G677.00 Occlusion/stenosis cerebral arts not result cerebral infarct





Gyu6500 [X]Occlusion and stenosis of other precerebral arteries

SP01200 Mechanical complication of carotid artery bypass

14NB.00 H/O: Peripheral vascular disease procedure

662U.00 Peripheral vascular disease monitoring

9m1..00 Peripheral vascular disease monitoring invitation

9N4h.00 DNA - Did not attend peripheral vascular disease c

G63..00 Precerebral arterial occlusion

G63..12 Stenosis of precerebral arteries

G70..00 Atherosclerosis

G70..11 Arteriosclerosis

G700.00 Aortic atherosclerosis

G700.11 Aorto-iliac disease

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G702.00 Extremity artery atheroma

G702000 Monckeberg's medial sclerosis

G70z.00 Arteriosclerotic vascular disease NOS

G73..00 Other peripheral vascular disease

G73..11 Peripheral ischaemic vascular disease

G73..12 Ischaemia of legs

G73..13 Peripheral ischaemia

G733.00 Ischaemic foot

G734.00 Peripheral arterial disease

G73y.00 Other specified peripheral vascular disease

G73yz00 Other specified peripheral vascular disease NOS

G73z.00 Peripheral vascular disease NOS

G73z000 Intermittent claudication

G73z011 Claudication

G73z012 Vascular claudication

G73zz00 Peripheral vascular disease NOS

G784.00 Occlusion of artery of lower limb

G784000 Occlusion of dorsalis pedis artery

G784100 Occlusion of anterior tibial artery

G784200 Occlusion of posterior tibial artery

Gyu7400 [X]Other specified peripheral vascular diseases

Non-ASCVD

T2DM

66A3.00 Diabetic on diet only

66A4.00 Diabetic on oral treatment

66Ao.00 Diabetes type 2 review

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66At100 Type II diabetic dietary review


C100100 Diabetes mellitus, adult onset, no mention of comp

C100111 Maturity onset diabetes

C100112 Non-insulin dependent diabetes mellitus

C101100 Diabetes mellitus, adult onset, with ketoacidosis

C102.00 Diabetes mellitus with hyperosmolar coma

C102100 Diabetes mellitus, adult onset, with hyperosmolar

C103100 Diabetes mellitus, adult onset, with ketoacidotic

C105100 Diabetes mellitus, adult onset, + ophthalmic manif

C106100 Diabetes mellitus, adult onset, + neurological man

C107100 Diabetes mellitus, adult, + peripheral circulatory

C107200 Diabetes mellitus, adult with gangrene

C109.00 Non-insulin dependent diabetes mellitus

C109.11 NIDDM - Non-insulin dependent diabetes mellitus


C109.13 Type II diabetes mellitus

C109200 Non-insulin-dependent diabetes mellitus with neuro

C109211 Type II diabetes mellitus with neurological compli


C109300 Non-insulin-dependent diabetes mellitus with multi

C109311 Type II diabetes mellitus with multiple complicati


C109400 Non-insulin dependent diabetes mellitus with ulcer

C109411 Type II diabetes mellitus with ulcer


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C109500 Non-insulin dependent diabetes mellitus with gangr

C109511 Type II diabetes mellitus with gangrene


C109700 Non-insulin dependent diabetes mellitus - poor con

C109711 Type II diabetes mellitus - poor control


C109900 Non-insulin-dependent diabetes mellitus without co

C109911 Type II diabetes mellitus without complication

C109912 Type 2 diabetes mellitus without complication

C109A00 Non-insulin dependent diabetes mellitus with monon

C109A11 Type II diabetes mellitus with mononeuropathy

C109A12 Type 2 diabetes mellitus with mononeuropathy

C109B00 Non-insulin dependent diabetes mellitus with polyn

C109B11 Type II diabetes mellitus with polyneuropathy

C109B12 Type 2 diabetes mellitus with polyneuropathy

C109D00 Non-insulin dependent diabetes mellitus with hypog

C109D11 Type II diabetes mellitus with hypoglycaemic coma

C109D12 Type 2 diabetes mellitus with hypoglycaemic coma

C109E00 Non-insulin depend diabetes mellitus with diabetic

C109E11 Type II diabetes mellitus with diabetic cataract

C109E12 Type 2 diabetes mellitus with diabetic cataract

C109F11 Type II diabetes mellitus with peripheral angiopat

C109F12 Type 2 diabetes mellitus with peripheral angiopath

C109G00 Non-insulin dependent diabetes mellitus with arthr

C109G11 Type II diabetes mellitus with arthropathy

C109G12 Type 2 diabetes mellitus with arthropathy

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C109H11 Type II diabetes mellitus with neuropathic arthrop

C109H12 Type 2 diabetes mellitus with neuropathic arthropa

C109J00 Insulin treated Type 2 diabetes mellitus

C109J11 Insulin treated non-insulin dependent diabetes mel

C109J12 Insulin treated Type II diabetes mellitus

C109K00 Hyperosmolar non-ketotic state in type 2 diabetes

C10C.00 Diabetes mellitus autosomal dominant

C10C.11 Maturity onset diabetes in youth

C10D.00 Diabetes mellitus autosomal dominant type 2

C10D.11 Maturity onset diabetes in youth type 2

C10F.00 Type 2 diabetes mellitus

C10F.11 Type II diabetes mellitus

C10F200 Type 2 diabetes mellitus with neurological complic

C10F211 Type II diabetes mellitus with neurological compli

C10F300 Type 2 diabetes mellitus with multiple complicatio

C10F311 Type II diabetes mellitus with multiple complicati

C10F400 Type 2 diabetes mellitus with ulcer

C10F411 Type II diabetes mellitus with ulcer

C10F500 Type 2 diabetes mellitus with gangrene

C10F511 Type II diabetes mellitus with gangrene

C10F700 Type 2 diabetes mellitus - poor control

C10F711 Type II diabetes mellitus - poor control

C10F900 Type 2 diabetes mellitus without complication

C10F911 Type II diabetes mellitus without complication

C10FA00 Type 2 diabetes mellitus with mononeuropathy

C10FA11 Type II diabetes mellitus with mononeuropathy

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C10FB00 Type 2 diabetes mellitus with polyneuropathy

C10FB11 Type II diabetes mellitus with polyneuropathy

C10FD00 Type 2 diabetes mellitus with hypoglycaemic coma

C10FD11 Type II diabetes mellitus with hypoglycaemic coma

C10FE00 Type 2 diabetes mellitus with diabetic cataract

C10FE11 Type II diabetes mellitus with diabetic cataract

C10FF00 Type 2 diabetes mellitus with peripheral angiopath

C10FF11 Type II diabetes mellitus with peripheral angiopat

C10FG00 Type 2 diabetes mellitus with arthropathy

C10FG11 Type II diabetes mellitus with arthropathy

C10FH00 Type 2 diabetes mellitus with neuropathic arthropa

C10FH11 Type II diabetes mellitus with neuropathic arthrop

C10FJ00 Insulin treated Type 2 diabetes mellitus

C10FJ11 Insulin treated Type II diabetes mellitus

C10FK00 Hyperosmolar non-ketotic state in type 2 diabetes

C10FK11 Hyperosmolar non-ketotic state in type II diabetes

C10FN00 Type 2 diabetes mellitus with ketoacidosis

C10FN11 Type II diabetes mellitus with ketoacidosis

C10FP00 Type 2 diabetes mellitus with ketoacidotic coma

C10FP11 Type II diabetes mellitus with ketoacidotic coma

C10FR00 Type 2 diabetes mellitus with gastroparesis

C10FR11 Type II diabetes mellitus with gastroparesis

C10FS00 Maternally inherited diabetes mellitus

C10N.00 Secondary diabetes mellitus

C10N000 Secondary diabetes mellitus without complication

C10y100 Diabetes mellitus, adult, + other specified manife

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C10z100 Diabetes mellitus, adult onset, + unspecified comp

L180600 Pre-existing diabetes mellitus, non-insulin-depend

C104100 Diabetes mellitus, adult onset, with renal manifes

C109000 Non-insulin-dependent diabetes mellitus with renal

C109011 Type II diabetes mellitus with renal complications


C109C00 Non-insulin dependent diabetes mellitus with nephr

C109C11 Type II diabetes mellitus with nephropathy

C109C12 Type 2 diabetes mellitus with nephropathy

C10F000 Type 2 diabetes mellitus with renal complications

C10F011 Type II diabetes mellitus with renal complications

C10FC00 Type 2 diabetes mellitus with nephropathy

C10FC11 Type II diabetes mellitus with nephropathy

C10FL00 Type 2 diabetes mellitus with persistent proteinur

C10FL11 Type II diabetes mellitus with persistent proteinu

C10FM00 Type 2 diabetes mellitus with persistent microalbu

C10FM11 Type II diabetes mellitus with persistent microalb

C109100 Non-insulin-dependent diabetes mellitus with ophth

C109111 Type II diabetes mellitus with ophthalmic complica


C109600 Non-insulin-dependent diabetes mellitus with retin

C109611 Type II diabetes mellitus with retinopathy


C10F100 Type 2 diabetes mellitus with ophthalmic complicat

C10F111 Type II diabetes mellitus with ophthalmic complica

C10F600 Type 2 diabetes mellitus with retinopathy

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C10F611 Type II diabetes mellitus with retinopathy

C10FQ00 Type 2 diabetes mellitus with exudative maculopath

C10FQ11 Type II diabetes mellitus with exudative maculopat

T1DM

66An.00 Diabetes type 1 review

66At000 Type I diabetic dietary review


66AV.00 Diabetic on insulin and oral treatment

C100000 Diabetes mellitus, juvenile type, no mention of co

C100011 Insulin dependent diabetes mellitus

C101000 Diabetes mellitus, juvenile type, with ketoacidosi

C102000 Diabetes mellitus, juvenile type, with hyperosmola

C103000 Diabetes mellitus, juvenile type, with ketoacidoti

C105000 Diabetes mellitus, juvenile type, + ophthalmic man

C106000 Diabetes mellitus, juvenile, + neurological manife

C107000 Diabetes mellitus, juvenile +peripheral circulator

C108.00 Insulin dependent diabetes mellitus

C108.11 IDDM-Insulin dependent diabetes mellitus


C108.13 Type I diabetes mellitus

C108200 Insulin-dependent diabetes mellitus with neurologi

C108211 Type I diabetes mellitus with neurological complic


C108300 Insulin dependent diabetes mellitus with multiple

C108311 Type I diabetes mellitus with multiple complicatio


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C108400 Unstable insulin dependent diabetes mellitus

C108411 Unstable type I diabetes mellitus

C108412 Unstable type 1 diabetes mellitus

C108500 Insulin dependent diabetes mellitus with ulcer

C108511 Type I diabetes mellitus with ulcer


C108600 Insulin dependent diabetes mellitus with gangrene

C108611 Type I diabetes mellitus with gangrene


C108800 Insulin dependent diabetes mellitus - poor control

C108811 Type I diabetes mellitus - poor control


C108900 Insulin dependent diabetes maturity onset

C108911 Type I diabetes mellitus maturity onset

C108912 Type 1 diabetes mellitus maturity onset

C108A00 Insulin-dependent diabetes without complication

C108A11 Type I diabetes mellitus without complication

C108A12 Type 1 diabetes mellitus without complication

C108B00 Insulin dependent diabetes mellitus with mononeuro

C108B11 Type I diabetes mellitus with mononeuropathy

C108B12 Type 1 diabetes mellitus with mononeuropathy

C108C00 Insulin dependent diabetes mellitus with polyneuro

C108C11 Type I diabetes mellitus with polyneuropathy

C108C12 Type 1 diabetes mellitus with polyneuropathy

C108E00 Insulin dependent diabetes mellitus with hypoglyca

C108E11 Type I diabetes mellitus with hypoglycaemic coma

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C108E12 Type 1 diabetes mellitus with hypoglycaemic coma

C108F00 Insulin dependent diabetes mellitus with diabetic

C108F11 Type I diabetes mellitus with diabetic cataract

C108F12 Type 1 diabetes mellitus with diabetic cataract

C108G11 Type I diabetes mellitus with peripheral angiopath

C108G12 Type 1 diabetes mellitus with peripheral angiopath

C108H00 Insulin dependent diabetes mellitus with arthropat

C108H11 Type I diabetes mellitus with arthropathy

C108H12 Type 1 diabetes mellitus with arthropathy

C108J11 Type I diabetes mellitus with neuropathic arthropa

C108J12 Type 1 diabetes mellitus with neuropathic arthropa

C10C.12 Maturity onset diabetes in youth type 1

C10E.00 Type 1 diabetes mellitus

C10E.11 Type I diabetes mellitus

C10E.12 Insulin dependent diabetes mellitus

C10E200 Type 1 diabetes mellitus with neurological complic

C10E211 Type I diabetes mellitus with neurological complic

C10E212 Insulin-dependent diabetes mellitus with neurologi

C10E300 Type 1 diabetes mellitus with multiple complicatio

C10E311 Type I diabetes mellitus with multiple complicatio

C10E312 Insulin dependent diabetes mellitus with multiple

C10E400 Unstable type 1 diabetes mellitus

C10E411 Unstable type I diabetes mellitus

C10E412 Unstable insulin dependent diabetes mellitus

C10E500 Type 1 diabetes mellitus with ulcer

C10E511 Type I diabetes mellitus with ulcer

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C10E512 Insulin dependent diabetes mellitus with ulcer

C10E600 Type 1 diabetes mellitus with gangrene

C10E611 Type I diabetes mellitus with gangrene

C10E612 Insulin dependent diabetes mellitus with gangrene

C10E800 Type 1 diabetes mellitus - poor control

C10E811 Type I diabetes mellitus - poor control

C10E812 Insulin dependent diabetes mellitus - poor control

C10E900 Type 1 diabetes mellitus maturity onset

C10E911 Type I diabetes mellitus maturity onset

C10E912 Insulin dependent diabetes maturity onset

C10EA00 Type 1 diabetes mellitus without complication

C10EA11 Type I diabetes mellitus without complication

C10EA12 Insulin-dependent diabetes without complication

C10EB00 Type 1 diabetes mellitus with mononeuropathy

C10EB11 Type I diabetes mellitus with mononeuropathy

C10EB12 Insulin dependent diabetes mellitus with mononeuro

C10EC00 Type 1 diabetes mellitus with polyneuropathy

C10EC11 Type I diabetes mellitus with polyneuropathy

C10EC12 Insulin dependent diabetes mellitus with polyneuro

C10EE00 Type 1 diabetes mellitus with hypoglycaemic coma

C10EE11 Type I diabetes mellitus with hypoglycaemic coma

C10EE12 Insulin dependent diabetes mellitus with hypoglyca

C10EF00 Type 1 diabetes mellitus with diabetic cataract

C10EF11 Type I diabetes mellitus with diabetic cataract

C10EF12 Insulin dependent diabetes mellitus with diabetic

C10EG00 Type 1 diabetes mellitus with peripheral angiopath

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C10EG11 Type I diabetes mellitus with peripheral angiopath

C10EH00 Type 1 diabetes mellitus with arthropathy

C10EH11 Type I diabetes mellitus with arthropathy

C10EH12 Insulin dependent diabetes mellitus with arthropat

C10EJ00 Type 1 diabetes mellitus with neuropathic arthropa

C10EJ11 Type I diabetes mellitus with neuropathic arthropa

C10EK00 Type 1 diabetes mellitus with persistent proteinur

C10EK11 Type I diabetes mellitus with persistent proteinur

C10EL00 Type 1 diabetes mellitus with persistent microalbu

C10EL11 Type I diabetes mellitus with persistent microalbu

C10EM00 Type 1 diabetes mellitus with ketoacidosis

C10EM11 Type I diabetes mellitus with ketoacidosis

C10EN00 Type 1 diabetes mellitus with ketoacidotic coma

C10EN11 Type I diabetes mellitus with ketoacidotic coma

C10EQ00 Type 1 diabetes mellitus with gastroparesis

C10EQ11 Type I diabetes mellitus with gastroparesis

C10y000 Diabetes mellitus, juvenile, + other specified man

C10z000 Diabetes mellitus, juvenile type, + unspecified co

L180500 Pre-existing diabetes mellitus, insulin-dependent

C104000 Diabetes mellitus, juvenile type, with renal manif

C108000 Insulin-dependent diabetes mellitus with renal com

C108011 Type I diabetes mellitus with renal complications


C108D00 Insulin dependent diabetes mellitus with nephropat

C108D11 Type I diabetes mellitus with nephropathy

C108D12 Type 1 diabetes mellitus with nephropathy

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C10E000 Type 1 diabetes mellitus with renal complications

C10E011 Type I diabetes mellitus with renal complications

C10E012 Insulin-dependent diabetes mellitus with renal com

C10ED00 Type 1 diabetes mellitus with nephropathy

C10ED11 Type I diabetes mellitus with nephropathy

C10ED12 Insulin dependent diabetes mellitus with nephropat

C108100 Insulin-dependent diabetes mellitus with ophthalmi

C108111 Type I diabetes mellitus with ophthalmic complicat


C108700 Insulin dependent diabetes mellitus with retinopat

C108711 Type I diabetes mellitus with retinopathy


C10E100 Type 1 diabetes mellitus with ophthalmic complicat

C10E111 Type I diabetes mellitus with ophthalmic complicat

C10E112 Insulin-dependent diabetes mellitus with ophthalmi

C10E700 Type 1 diabetes mellitus with retinopathy

C10E711 Type I diabetes mellitus with retinopathy

C10E712 Insulin dependent diabetes mellitus with retinopat

C10EP00 Type 1 diabetes mellitus with exudative maculopath

C10EP11 Type I diabetes mellitus with exudative maculopath

CKD

1Z12.00 Chronic kidney disease stage 3

1Z15.00 Chronic kidney disease stage 3A

1Z16.00 Chronic kidney disease stage 3B

1Z1B.00 Chronic kidney disease stage 3 with proteinuria

1Z1B.11 CKD stage 3 with proteinuria

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1Z1C.00 Chronic kidney disease stage 3 without proteinuria

1Z1C.11 CKD stage 3 without proteinuria

1Z1D.00 Chronic kidney disease stage 3A with proteinuria

1Z1D.11 CKD stage 3A with proteinuria

1Z1E.00 Chronic kidney disease stage 3A without proteinuria

1Z1E.11 CKD stage 3A without proteinuria

1Z1F.00 Chronic kidney disease stage 3B with proteinuria

1Z1F.11 CKD stage 3B with proteinuria

1Z1G.00 Chronic kidney disease stage 3B without proteinuria

1Z1G.11 CKD stage 3B without proteinuria


1Z1H.00 Chronic kidney disease stage 4 with proteinuria

1Z1H.11 CKD stage 4 with proteinuria

1Z1J.00 Chronic kidney disease stage 4 without proteinuria

1Z1J.11 CKD stage 4 without proteinuria


1Z1K.00 Chronic kidney disease stage 5 with proteinuria

1Z1K.11 CKD stage 5 with proteinuria

1Z1L.00 Chronic kidney disease stage 5 without proteinuria

1Z1L.11 CKD stage 5 without proteinuria

7L1A.11 Dialysis for renal failure

7L1A000 Renal dialysis

7L1A100 Peritoneal dialysis

7L1A200 Haemodialysis NEC

7L1A400 Automated peritoneal dialysis

7L1A500 Continuous ambulatory peritoneal dialysis

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7L1A600 Peritoneal dialysis NEC


SP06B00 Continuous ambulatory peritoneal dialysis associated perit

SP0E.00 Disorders associated with peritoneal dialysis

K05..12 End stage renal failure

K050.00 End stage renal failure


disease; CKD, chronic kidney disease; PAD, peripheral arterial disease; T1DM, type 1 diabetes mellitus;

T2DM, type 1 diabetes mellitus

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SUPPLEMENTAL TABLE S2. Categorisation of Lipid Modifying Therapy (LMT)

High-intensity statin Atorvastatin 20, 40, and 80 mg; rosuvastatin 10, 20, and 40 mg; simvastatin 80

mg

Medium-intensity statin Atorvastatin 10 mg; rosuvastatin 5 mg; simvastatin 20 and 40 mg; fluvastatin

80 mg

Low-intensity statin Simvastatin 10 mg; pravastatin 10, 20, and 40 mg; fluvastatin 20 and 40 mg

Nonstatin LMT Ezetimibe, nicotinic acid (niacin, acipimox), fibrates (benzafibrate, ciprofibrate,

fenofibrate, and gemfibrozil), bile acid sequestrants (cholestyramine,

colesevelam, and colestipol)

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SUPPLEMENTAL TABLE S3. Baseline Characteristics for the Overall ASCVD

Cohort and Prevalent Subgroups

Recent ACS

(n = 3112)



PAD (n = 19 830)

Total ASCVD

(n = 91 479)


Age, mean, years (SD) 67.8 (12.8) 72.6 (10.6) 73.9 (11.5) 73.5 (10.3) 72.6 (10.9)

Male, % 66.5 63.7 52.3 65.4 60.7


2.7 (1.4)

2.7 (1.4)

2.6 (1.4)

2.8 (1.4)

2.7 (1.4)

Ethnicity, %

White 28.3 30.3 29.5 30.6 30.0

South Asian† 15.1 14.0 13.8 12.9 13.9

Black Caribbean / African

0.3 0.3 0.5 0.4 0.3

Chinese 0.0 0.1 0.1 0.1 0.1

Not recorded 56.4 55.4 56.1 56.1 55.8

Current smoker, % 15.2 12.1 13.5 26.6 14.1

BMI, mean, kg/m2 (SD) 28.4 (5.4) 28.5 (5.3) 27.8 (5.4) 27.7 (5.3) 28.3 (5.4)

Systolic BP, mean (SD)

128.9 (17.8)

131.4 (15.8)

132.8 (16.0)

133.5 (16.4)

132.1 (15.9)


Recent ACS, % 100.0 3.3 0.9 1.6 3.4

Other CHD, % 64.2 100.0 24.0 34.0 66.0

Ischaemic stroke / TIA, %

7.6 10.4 100.0 21.5 28.6

PAD, % 10.1 11.2 16.3 100.0 21.7

DM, % 27.0 30.0 27.3 34.5 29.4

Hypertension, % 50.4 61.2 64.0 66.7 61.5

History of CHF, % 14.0 11.3 6.9 8.9 9.1

CKD stage III 17.2 24.4 22.1 23.0 23.5

CKD stage IV- V‡ 0.2 0.3 0.2 0.4 0.2

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Beta-blockers, % 81.4 60.1 23.5 22.4 48.7

ACEI/ARBs, % 85.0 65.3 52.1 52.4 61.7

Antiplatelets,# % 52.5 13.5 29.7 15.4 18.5

* Social deprivation index is defined by Townsend deprivation index score, 1 = most affluent and 5 = least

affluent;

† Includes Indian, Pakistani, Bangladeshi, and other South Asian individuals; ‡ Stage V CKD includes

end-stage renal disease and dialysis. ¶ Medication use on index date. # Clopidogrel/ticagrelor/prasugrel

ACEI, angiotensin converting enzyme inhibitor; ACS, acute coronary syndrome; ARB, angiotensin II

receptor blocker; ASCVD, atherosclerotic cardiovascular disease; BMI, body-mass index; BP, blood

pressure; CHD, coronary heart disease; CHF, congestive heart failure; CKD, chronic kidney disease; DM,

diabetes mellitus; PAD, peripheral arterial disease; SD, standard deviation; TIA, transient ischaemic

attack

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SUPPLEMENTAL TABLE S4. Use of LMT in the Overall ASCVD Cohort and

Prevalent Subgroups

Recent ACS

(n = 3112)



PAD (n = 19 830)

Total ASCVD

(n = 91 479)

High-intensity statin, % 62.4 35.5 24.7 30.2 31.4

Monotherapy, % 93.3 91.9 92.6 91.1 92.2

Plus Ezetimibe, % 1.0 4.5 3.5 4.7 4.1


Medium-intensity statin, % 22.6 40.7 44.8 42.8 42.1

Monotherapy, % 98.6 97.9 98.4 98.4 98.2

Plus Ezetimibe, % 0.6 1.2 0.9 0.8 1.0


Low-intensity statin, % 2.1 5.7 5.8 5.4 5.6

Monotherapy, % 93.8 95.8 96.6 96.3 96.3

Plus Ezetimibe, % 6.3 3.3 2.6 3.0 2.8


Nonstatins only, % 0.9 2.0 1.8 1.9 1.9

Ezetimibe, monotherapy, % 70.4 61.5 65.4 60.1 61.6

Other nonstatin LMT, % 29.6 38.5 34.6 39.9 38.4

Not currently treated by LMT, % 12.1 16.0 22.9 19.7 19.0


20.7 16.7 10.1 12.7 13.2


22.8 40.5 38.9 36.7 38.4


5.6 9.9 7.7 7.6 8.5

Previously on nonstatin LMT, % 4.8 7.2 5.6 5.7 5.9

No previous LMT, % 46.1 25.7 37.7 37.3 34.0

Numbers in the grey bars denote absolute percentages, and add up to 100% vertically. Numbers in the

white bars are relative percentages of the absolute percentages in the grey bars.


disease; LMT, lipid modifying therapy; PAD, peripheral arterial disease; TIA, transient ischaemic attack

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ASCVD Cohort and Prevalent Subgroups

Recent ACS

(n = 3112)



PAD (n = 10 234)

Total ASCVD

(n = 91 479)

Mean LDL-C, mmol/L





No current LMT 2.9 3.1 3.1 3.1 3.1

Total 2.0 2.2 2.3 2.4 2.3






No current LMT 14.9 8.7 6.5 7.4 8.0

Total 43.9 31.5 27.9 26.4 30.6






No current LMT 3.6 3.7 3.8 3.8 3.8

Total 2.6 2.9 3.0 3.1 2.9






No current LMT 20.7 14.9 13.8 13.6 14.5

Total 54.8 42.6 41.0 36.9 42.0




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ASCVD Cohort and Hierarchical Subgroups

Recent ACS

(n = 3112)



PAD (n = 19 830)

Total ASCVD

(n = 91 479)

Mean LDL-C, mmol/L





No current LMT 2.9 3.1 3.1 3.1 3.1

Total 2.0 2.2 2.3 2.3 2.3






No current LMT 14.9 8.9 7.0 8.4 8.0

Total 43.8 32.0 28.4 26.4 30.6






No current LMT 3.6 3.7 3.8 3.7 3.8

Total 2.6 2.9 3.0 3.0 2.9






No current LMT 20.7 15.0 14.3 14.9 14.5

Total 54.5 43.0 41.5 36.9 42.0




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SUPPLEMENTAL TABLE S7. Lipid Level Achievement by LMT in the Overall Non-

ASCVD Cohort and Subgroups

T2DM and QRISK2

>10% with CKD

(n = 11 102)

T2DM and QRISK 2

>10% without

CKD (n = 52

556)

T1DM and age >40

years with CKD

(n = 749)

T1DM and age >40 years

without CKD

(n = 4204)

CKD without

DM criteria (n = 23

475)

Total non-ASCVD (n = 92

086)

Mean LDL-C, mmol/L





No current LMT 2.9 3.0 2.7 2.7 3.3 3.1

Total 2.2 2.4 2.1 2.3 2.8 2.4






No current LMT 10.3 7.5 17.6 11.5 3.7 6.7

Total 35.7 28.4 39.8 25.9 15.7 26.0






No current LMT 3.6 3.8 3.3 3.2 3.9 3.8

Total 2.94 3.1 2.7 2.9 3.4 3.2






No current LMT 16.1 12.1 26.8 26.2 8.5 11.9

Total 41.9 34.3 52.0 43.2 24.3 33.2

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ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; HDL-C, high-density

lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LMT, lipid modifying therapy; T1DM,

type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus

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The RECORD statement – checklist of items, extended from the STROBE statement, that should be reported in observational studies using

routinely collected health data.

Item

No.

STROBE items Location in

manuscript where

items are reported

RECORD items Location in

manuscript

where items are

reported

Title and abstract

1 (a) Indicate the study’s design

with a commonly used term in

the title or the abstract (b)

Provide in the abstract an

informative and balanced

summary of what was done and

what was found

Abstract p3

RECORD 1.1: The type of data used

should be specified in the title or

abstract. When possible, the name of

the databases used should be included.

RECORD 1.2: If applicable, the

geographic region and timeframe within

which the study took place should be

reported in the title or abstract.

RECORD 1.3: If linkage between

databases was conducted for the study,

this should be clearly stated in the title

or abstract.

Abstract p3

Abstract p3

Not applicable

(n/a)

Introduction

Background

rationale

2 Explain the scientific background

and rationale for the investigation

being reported


Objectives 3 State specific objectives,

including any prespecified

hypotheses


Methods

Study Design 4 Present key elements of study

design early in the paper


Setting 5 Describe the setting, locations,

and relevant dates, including

periods of recruitment, exposure,

follow-up, and data collection


Participants 6 (a) Cohort study - Give the


Methods p7-11 plus

supplemental files

RECORD 6.1: The methods of study

population selection (such as codes or

Methods p7-11

plus supplemental

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of participants. Describe methods

of follow-up

Case-control study - Give the


sources and methods of case

ascertainment and control

selection. Give the rationale for

the choice of cases and controls

Cross-sectional study - Give the



of participants

(b) Cohort study - For matched


and number of exposed and

unexposed

Case-control study - For matched


and the number of controls per

case

algorithms used to identify subjects)

should be listed in detail. If this is not

possible, an explanation should be

provided.

RECORD 6.2: Any validation studies

of the codes or algorithms used to select

the population should be referenced. If

validation was conducted for this study

and not published elsewhere, detailed

methods and results should be provided.

RECORD 6.3: If the study involved

linkage of databases, consider use of a

flow diagram or other graphical display

to demonstrate the data linkage process,

including the number of individuals

with linked data at each stage.

files

Supplement

n/a

Variables 7 Clearly define all outcomes,

exposures, predictors, potential

confounders, and effect

modifiers. Give diagnostic

criteria, if applicable.

Methods p7-11 plus

supplemental files

RECORD 7.1: A complete list of codes

and algorithms used to classify

exposures, outcomes, confounders, and

effect modifiers should be provided. If

these cannot be reported, an explanation

should be provided.

Supplement

Data sources/

measurement

8 For each variable of interest, give

sources of data and details of

methods of assessment

(measurement).

Describe comparability of

assessment methods if there is

more than one group


Bias 9 Describe any efforts to address

potential sources of bias

Addressed in Results

p15 and Discussion

p21

Addressed in

Results p15 and

Discussion p21

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Study size 10 Explain how the study size was

arrived at


Quantitative

variables

11 Explain how quantitative

variables were handled in the

analyses. If applicable, describe

which groupings were chosen,

and why


Statistical

methods

12 (a) Describe all statistical

methods, including those used to

control for confounding

(b) Describe any methods used to

examine subgroups and

interactions

(c) Explain how missing data

were addressed

(d) Cohort study - If applicable,

explain how loss to follow-up

was addressed

Case-control study - If

applicable, explain how matching

of cases and controls was

addressed

Cross-sectional study - If

applicable, describe analytical

methods taking account of

sampling strategy

(e) Describe any sensitivity

analyses

Methods p7-11, with

specific stats

methods on p10-11.

Methods p7-11,

with specific stats

methods on p10-

11.

Data access and

cleaning methods

.. P10, patient

involvement section

RECORD 12.1: Authors should

describe the extent to which the

investigators had access to the database

population used to create the study

population.


information on the data cleaning

methods used in the study.

P10, patient

involvement

section

As above

Linkage .. n/a RECORD 12.3: State whether the study n/a

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included person-level, institutional-

level, or other data linkage across two

or more databases. The methods of

linkage and methods of linkage quality

evaluation should be provided.

Results

Participants 13 (a) Report the numbers of

individuals at each stage of the

study (e.g., numbers potentially

eligible, examined for eligibility,

confirmed eligible, included in

the study, completing follow-up,

and analysed)

(b) Give reasons for non-

participation at each stage.

(c) Consider use of a flow

diagram

P12 and Figure 2 RECORD 13.1: Describe in detail the

selection of the persons included in the

study (i.e., study population selection)

including filtering based on data

quality, data availability and linkage.

The selection of included persons can

be described in the text and/or by means

of the study flow diagram.

P12 and Figure 2

Descriptive data 14 (a) Give characteristics of study

participants (e.g., demographic,

clinical, social) and information

on exposures and potential

confounders

(b) Indicate the number of

participants with missing data for

each variable of interest

(c) Cohort study - summarise

follow-up time (e.g., average and

total amount)

P12 P12

Outcome data 15 Cohort study - Report numbers of

outcome events or summary

measures over time

Case-control study - Report

numbers in each exposure

category, or summary measures

of exposure

Cross-sectional study - Report

numbers of outcome events or

summary measures

P12-15 P12-15

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Main results 16 (a) Give unadjusted estimates

and, if applicable, confounder-

adjusted estimates and their

precision (e.g., 95% confidence

interval). Make clear which

confounders were adjusted for

and why they were included

(b) Report category boundaries

when continuous variables were

categorized

(c) If relevant, consider

translating estimates of relative

risk into absolute risk for a

meaningful time period

P12-15 Results p12-15

Other analyses 17 Report other analyses done—e.g.,

analyses of subgroups and

interactions, and sensitivity

analyses

Results p12-15 Results p12-15

Discussion

Key results 18 Summarise key results with

reference to study objectives

P16 P16

Limitations 19 Discuss limitations of the study,

taking into account sources of

potential bias or imprecision.

Discuss both direction and

magnitude of any potential bias

P20 RECORD 19.1: Discuss the

implications of using data that were not

created or collected to answer the

specific research question(s). Include

discussion of misclassification bias,

unmeasured confounding, missing data,

and changing eligibility over time, as

they pertain to the study being reported.

P20

Interpretation 20 Give a cautious overall

interpretation of results

considering objectives,

limitations, multiplicity of

analyses, results from similar

studies, and other relevant

evidence

P16-20, summary on

p21

P16-20, summary

on p21

Generalisability 21 Discuss the generalisability

(external validity) of the study

P16-21 P16-21

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results

Other Information

Funding 22 Give the source of funding and

the role of the funders for the

present study and, if applicable,

for the original study on which

the present article is based

P22 P22

Accessibility of

protocol, raw

data, and

programming

code

.. Information provided

within supplement


information on how to access any

supplemental information such as the

study protocol, raw data, or

programming code.

Information

provided within

supplement

*Reference: Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, Sørensen HT, von Elm E, Langan SM, the RECORD Working

Committee. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLoS Medicine 2015;

in press.

*Checklist is protected under Creative Commons Attribution (CC BY) license.

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