Do statins affect risk of Do statins affect risk of pneumonia in the general pneumonia in the general

population: nested case control population: nested case control studystudy

Yana VinogradovaYana VinogradovaJulia Hippisley-Cox Julia Hippisley-Cox

CalgaryCalgary20072007

Aims of presentationAims of presentation

Research study Research study – Present analysis of study determining the

risk of community acquired pneumonia in patients taking statins

Background to pneumonia Background to pneumonia statin analysis statin analysis

• Some evidence from lab data that Some evidence from lab data that statins benefit in case of infectious statins benefit in case of infectious diseasesdiseases

• Statins can reduce rate of severe Statins can reduce rate of severe sepsis and ICU admissionsepsis and ICU admission

• Significant reduction in mortalitySignificant reduction in mortality

• Reduction in fatal pneumonia riskReduction in fatal pneumonia risk

• 51% reduction in diabetes patients51% reduction in diabetes patients

Study population: Study population: QRESEARCH databaseQRESEARCH database

• Currently largest database in the UKCurrently largest database in the UK• 537 UK practices537 UK practices• > 6 practices in every Strategic Health > 6 practices in every Strategic Health

Authority (administrative area)Authority (administrative area)• > 9 million patients including those who > 9 million patients including those who

died, left and still registereddied, left and still registered• > 30 million person years of observation> 30 million person years of observation

Data source: Data source: QRESEARCH databaseQRESEARCH database

• Patient level consolidated databasePatient level consolidated database

• Anonymised dataAnonymised data

• Longitudinal data for 15+ yearsLongitudinal data for 15+ years

• Derived from GP clinical recordsDerived from GP clinical records

• Validated against external and internal Validated against external and internal measuresmeasures

• Industry independent Industry independent

Study design & settingStudy design & setting

• Nested case control studyNested case control study• Study period Jan 1996-Dec 2005 Study period Jan 1996-Dec 2005 • Cases were incident community-Cases were incident community-

acquired pneumonia patientsacquired pneumonia patients• 5 controls matched by 5 controls matched by

– Age– Sex– Practice– Calendar year

Assessment of exposureAssessment of exposureanalysis restricted to subjects with at least 2 years of analysis restricted to subjects with at least 2 years of

prescribing dataprescribing data

• useuse:: at least 2 script in 12 months prior to the index date

• different types of statinsdifferent types of statinsatorvastatin pravastatin cerivastatinsimvastatin fluvastatin rosuvastatin

• time for the last prescriptiontime for the last prescription: : 28 days29-89 days90-365 days

Statistical analysisStatistical analysis

• Conditional logistic regressionConditional logistic regression

• Odds ratios + 95% CIOdds ratios + 95% CI

• Unadjusted & adjustedUnadjusted & adjusted

Confounding factorsConfounding factorsSocio-economic Socio-economic statusstatus

• Townsend quintiles

Body mass indexBody mass index• Less than 25 kg/m2• 25 to 29.9 kg/m2• 30 kg/m2 or more• BMI not recorded

Smoking statusSmoking status• Non-smoker• Smoker• not recorded

MorbiditiesMorbidities• List of comorbidites

recommended for pneumococcal vaccination

• Additional comorbidities limiting mobility or suppressing immune system

VaccinationsVaccinations• Influenza• pneumococcal

Risk group for pneumococcal vaccine Risk group for pneumococcal vaccine from current CMO guidancefrom current CMO guidance

• DiabetesDiabetes• Chronic heart diseaseChronic heart disease• Chronic renal diseaseChronic renal disease• Chronic respiratory diseaseChronic respiratory disease• AspleniaAsplenia• CSF ShuntCSF Shunt• Chronic liver diseaseChronic liver disease• Sickle cell or Coeliac diseaseSickle cell or Coeliac disease• Cochlear ImplantCochlear Implant• HIV/AIDSHIV/AIDS• ImmunosuppressedImmunosuppressed

New potential risk groupNew potential risk group• New conditions selected because New conditions selected because

– they limit the mobility

– or can be associated with immunosuppression

• Diseases includedDiseases included– Stroke or TIA

– Rheumatoid arthritis

– Parkinson’s disease

– Common cancers

– Multiple sclerosis

– Dementia

– Osteoporosis

SampleSample

34,098 incident cases of CAP 1995/2006

22,718 cases older than 44 years

17,757 cases with 2 years of medical records

11.0

7.6

29.7

17.8

1.80.7

30.4

14.1

0.8 0.3 0.3 0.2 0.1 0.0

15.1

10.4

0

5

10

15

20

25

30

Pro

por

tion

of p

atie

nts

(%

)

Diabetes Heart Renal Chest Liver SC/CD HIV Immunosup© QRESEARCH 2006 version 11

Proportions of patients with current risk group diseases

cases controls

13.5

7.6

3.3

1.6 2.21.1 0.7 0.2

4.1

1.6

5.2

3.1

9.7

6.0

0

5

10

15

20

25

30

Pro

por

tion

of p

atie

nts

(%

)

Stroke RA Parkinson MS Dementia OP Any cancer© QRESEARCH 2006 version 11

Proportions of patients with additional risk group diseases

cases controls

Immunosuppressed

Sickle cell/ Coeliac disiase

Liver disease

Respiratory disease

Renal disease

Heart disease

Diabetes

1 1.5 2 2.5 3Adjusted for deprivation, smoking, years of data, use of flu and pneumo vaccines, all diseases and statins© QRESEARCH 2006 version 11

all patientsAdjusted odds ratios and 95% confidence intervals for current risk group

Any cancer

Osteoporosis

Dementia

Multiple sclerosis

Parkinson's disease

Rheumatoid arthritis

Stroke/TIA

1 1.5 2 2.5 3 3.5 4 4.5 5Adjusted for deprivation, smoking, years of data, use of flu and pneumo vaccines, all diseases and statins© QRESEARCH 2006 version 11

all patientsAdjusted odds ratios and 95% confidence intervals for additional risk group

Use of statin in the last 12 monthsUse of statin in the last 12 months

Cases Cases

N=17,757N=17,757

ControlsControls

N=80,487N=80,487

Unadjusted Unadjusted Odds RatioOdds Ratio

(95% CI)(95% CI)

Adjusted Adjusted Odds Ratio Odds Ratio

(95% CI)(95% CI) 2,244 2,244

(12.6%)(12.6%)

8,7888,788

(10.9%)(10.9%)

1.241.24

(1.18 – 1.31)(1.18 – 1.31)

0.820.82

(0.77 – 0.87)(0.77 – 0.87)

Adjusted for socio-economic status, body-mass index, Adjusted for socio-economic status, body-mass index, smoking status, use of influenza and pneumococcal smoking status, use of influenza and pneumococcal vaccinations and the co-morbidities vaccinations and the co-morbidities

4.44.0

0.1 0.10.4 0.4

1.1 0.9

6.6

5.5

0.1 0.00

1

2

3

4

5

6

7

8

9

Pro

por

tion

of p

atie

nts

(%

)

Atorvastatin Cerivastatin Fluvastatin Pravastatin Simavastatin Rosuvastatin© QRESEARCH 2006 version 11

Proportions of patients taking different statins

cases controls

1

.25

.5

.75

1

1.25

1.5

1.75

2

Atorvastatin Cerivastatin Fluvastatin Pravastatin Simavastatin Rosuvastatin

Odds ratio lower/upper limits of 95%CI

Adj

uste

d O

dds

Rat

io

4.4/ 4.0% 0.1/ 0.1% 0.4/ 0.4% 1.1/ 0.9% 6.6/ 5.5% 0.1/ 0.0%

785/ 3187 25/ 93 63/ 291 188/ 743 1174/ 4438 9/ 36

copyright QRESEARCH 2007

N of cases/ N of controls:

Adjusted odds ratios for use of different statins

7.47.1

4.1

3.0

1.10.8

0

1

2

3

4

5

6

7

8

9

10

Pro

port

ion

of p

atie

nts

(%)

1-28d 29-89d 90-365d

Proportions of statin users

cases

controls

1

.5

.6

.7

.8

.9

1

1.1

1.2

Ad

just

ed

Odd

s R

atio

1-28d 29-89d 90-365d

Adjusted odds ratios and 95% CI

Odds ratios adjusted for deprivation, smoking,use of flu and pneumococcal vaccines, risk groups© QRESEARCH 2006 version 11

Last prescription of statin

Main findingsMain findings

any use of statin: any use of statin:

• 13% to 23% decrease of pneumonia 13% to 23% decrease of pneumonia riskrisk

use of statin within the last 28 days: use of statin within the last 28 days:

• 22% to 32% decrease of risk22% to 32% decrease of risk

Methodological strengthsMethodological strengths

• Large sample size and representative Large sample size and representative populationpopulation

• Data electronically collected – Data electronically collected – unlikely misclassification bias unlikely misclassification bias

• Data collected before the diagnosis – Data collected before the diagnosis – no recall biasno recall bias

Methodological weaknessesMethodological weaknesses

• Misclassification bias: no x-ray or Misclassification bias: no x-ray or microbiological confirmationmicrobiological confirmation

• Misclassification of use: over-the-Misclassification of use: over-the-counter purchasecounter purchase

• Data contain information on Data contain information on prescription, not actual useprescription, not actual use

• Information on certain risk factors Information on certain risk factors (alcohol intake) (alcohol intake)

• Missing data for BMI, smokingMissing data for BMI, smoking

ConclusionsConclusions

• Recent use of statin is associated with Recent use of statin is associated with reduced risk of community acquired reduced risk of community acquired pneumoniapneumonia

AcknowledgementsAcknowledgements

QRESEARCH team QRESEARCH team – UoN– EMIS

Read codeTerm

H2 Pneumonia and influenza

H21 Lobar (pneumococcal) pneumonia

H21-1 Chest infection – pneumococcal pneumonia

H22 Other bacterial pneumonia

H22-1 Chest infection – other bacterial pneumonia

H223 Pneumonia due to streptococcus

H22yz Pneumonia due to bacteria NOS

H22z Bacterial pneumonia NOS

H23-1 Chest infection – pneumonia organism OS

H25 Bronchopneumonia due to unspecified organism

H25-1 Chest infection – unspecified bronchopneumonia

H26 Pneumonia due to unspecified organism

H260 Lobar pneumonia due to unspecified organism

H261 Basal pneumonia due to unspecified organism

H262 Postoperative pneumonia

H270 Influenza with pneumonia

H270-1 Chest infection – influenza with pneumonia

H2700 Influenza with bronchopneumonia

H2701 Influenza with pneumonia, influenza virus identified

H270z Influenza with pneumonia NOS

H28 Atypical pneumonia

H2y Other specified pneumonia or influenza

H2z Pneumonia or influenza NOS