the esc/eas guidelines

www.escardio.org/guidelines

The ESC/EAS Guidelinesfor the Management of Dyslipidaemias

and the AHA/ACC Guidelines

Alberico L. Catapano

www.escardio.org/guidelines European Heart Journal (2011) 32, 1769–1818

SCORE chart: 10 year risk of fatal cardiovascular

disease (CVD) in populations at low CVD risk

15% and over10%-14%5%-9%3%-4%2%1%< 1%

SCORE

10-year risk offatal CVD inpopulations atLow CVD risk

Non-smoker Smoker

180160140120 3

469

3469

35711

46812

471014

1234

1235

2246

2346

2357

180160140120 1

235

2245

2346

2357

3458

1123

1123

1123

1224

1234

180160140120 1

123

1123

1123

1234

1234

0111

0111

1112

1112

1112

180160140120 0

000

0000

0000

000 0

0000

0000

0000

0000

0000

0000

180160140120 0

111

0111

0112

1112

1112

0001

0001

0011

0011

0011

4 5 6 7 8 4 5 6 7 8

Women

Syst

olic

blo

od p

ress

ure

(mm

Hg)

Cholesterol (mmol/L)

Age

65

60

55

50

40

Non-smoker Smoker

Men

571015

581217

691420

8111623

9131926

2458

3469

35710

46812

571014

35710

45811

46913

571115

691318

2235

2346

2357

3458

3469

2346

2357

3468

35710

46812

1123

1224

1234

2235

2346

0011

0111

0111

111 2

1112

0000

0001

0001

0011

0011

1224

1234

2235

2346

2357

1112

1112

1123

1123

1224

4 5 6 7 8 4 5 6 7 8

150 200250 300mg/dl


Relative risk chart

European Heart Journal (2011) 32, 1769–1818

● This chart may be used to show younger people at low absolute risk that, relative to others in their age group, their risk may be many times higher than necessary. This may help to motivate decisions about avoidance of smoking, healthy nutrition and exercise, as well as flagging those who may become candidates for medication.

Please note that this chart shows RELATIVE not absolute risk. The risks are RELATIVE to 1 in the bottom left. Thus a person in the top right hand box has a risk that is 12 times higher than a person in the bottom left.

Non-smoker

180

160

140

120 2

3

4

6

2

3

5

7

3

4

6

8

3

5

7

10

4

6

8

12

1

1

2

3

1

2

3

3

1

2

3

4

2

2

4

5

2

3

4

6

4 5 6 7 8

Smoker

4 5 6 7 8

Cholesterol (mmol/L)

Systolic bloodpressure (mmHg)


Risk function without high-density lipoprotein-cholesterol (HDL-C)for women in populations at high cardiovascular disease risk

Non-smoker Smoker

180160140120 0

000

0000

0001

000 1

0001

0000

0000

0000

0000

0000

180160140120 1

111

1112

1112

1112

1122

0011

0011

0111

0111

0111

4 5 6 7 8 4 5 6 7 8

Total Cholesterol (mmol/L)

1112

1112

1122

112

11222

1223

1233

2234

223

22344

3457

3

57

3468

4568

4579

4 81014

681114

791215

791216

8101317

6

3456

3457

3457

3

68

4568

4

2234

2234

2234

223

23454

Age

65

60

55

50

40

180160140120

180160140120

180160140120

Without HDLHDL 0.8HDL 1.0HDL 1.4HDL 1.8

5.710.28.55.94.0


4.48.57.04.73.2


4.58.36.94.73.2


2.14.43.52.31.5


4.48.16.74.53.0


4.28.06.54.42.9


2.44.63.82.51.7

Systolic blood pressure (mmHg)


Qualifiers


● The charts can assist in risk assessment and management but must be interpreted in the light of the clinician’s knowledge and experience andof the patient’s pre-test likelihood of CVD.

● Risk will be overestimated in countries with a falling CVD mortality, andunderestimated in countries in which mortality is increasing.

● At any given age, risk estimates are lower for women than for men. This may be misleading since, eventually, at least as many women as men die of CVD. Inspection of the charts indicates that risk is merely deferred in women, with a 60-year-old woman resembling a 50-year-old man in terms of risk.


Risk will also be higher than indicated

in the charts in:● Socially deprived individuals; deprivation drives many other risk factors.

● Sedentary subjects and those with central obesity; these characteristics determine many of the other aspects of risk listed below.

● Individuals with diabetes: re-analysis of the SCORE database indicates that those with known diabetes are at greatly increased risk; five times higher in women and three times higher in men.

● Individuals with low HDL-C or apolipoprotein A1 (apo A1), increased TG, fibrinogen, homocysteine, apolipoprotein B (apo B), and lipoprotein(a) [Lp(a)] levels, familial hypercholesterolaemia (FH), or increased hs-CRP; these factors indicate a higher level of risk in both genders, all age groupsand at all levels of risk. As mentioned above, supplementary material (see Addendum I) illustrates the additional impact of HDL-C on risk estimation.

● Asymptomatic individuals with preclinical evidence of atherosclerosis, for example, the presence of plaques or increased carotid intima-media thickness (CIMT) on carotid ultrasonography.

● Those with impaired renal function.

● Those with a family history of premature CVD, which is considered to increase the risk by 1.7-fold in women and by 2.0-fold in men.

● Conversely, risk may be lower than indicated in those with very high HDL-C levels or a family history of longevity.


Intervention strategies as a function

of total CV risk and LDL-C levelTotal CV risk

(SCORE)%

LDL-C levels

< 70 mg/dL< 1.8 mmol/L

70 to < 100 mg/dL1.8 to < 2.5 mmol/L

100 to < 155 mg/dL2.5 to < 4.0 mmol/L

155 to < 190 mg/dL4.0 to < 4.9 mmol/L

> 190 mg/dL> 4.9 mmol/L

< 1 No lipid intervention No lipid intervention Lifestyle intervention Lifestyle interventionLifestyle intervention, consider drug if uncontrolled

Class/Level I/C I/C I/C I/C IIa/A

≥ 1 to < 5 Lifestyle intervention Lifestyle interventionLifestyle intervention, consider drug if uncontrolled

Lifestyle intervention, consider drug if uncontrolled

Lifestyle intervention, consider drug if uncontrolled

Class/Level I/C I/C IIa/A IIa/A I/A

> 5 to < 10, or high risk

Lifestyle interventionconsider drug*


Lifestyle interventionand immediate drug intervention


Lifestyle interventionand immediate drug

intervention

Class/Level IIa/A IIa/A IIa/A I/A I/A

≥ 10 or very high risk






Class/Level IIa/A IIa/A I/A I/A I/A


Recommendations for treatment targets

for LDL-CRecommendations Class Level

In patients at VERY HIGH CV risk (established CVD, type 2 diabetes, type 1 diabetes with target organ damage, moderate to severe CKD or a SCORE level ≥ 10%) the LDL-C goal is < 1.8 mmol/L (less than ~ 70 mg/dL) and/or ≥ 50% LDL-C reduction when target level cannot be reached.

I A

In patients at HIGH CV risk (markedly elevated single risk factors, a SCORE level ≥ 5 to < 10%) an LDL-C goal < 2.5 mmol/L (less than ~ 100 mg/dL) should be considered.

IIa A

In subjects at MODERATE risk (SCORE level > 1 to ≤ 5%) an LDL-C goal < 3.0 mmol/L (less than ~ 115 mg/dL) should be considered.

IIa C


To be preferred To be used withmoderation

To be chosen occasionnalyin limited amounts

Cereals Whole grains Refined bread, rice and pasta, biscuits, corn flakes

Pastries, muffins, pies, croissants

Vegetables Raw and cooked vegetables Vegetables prepared in butter or cream

Legumes All (including soy and soy protein)

Fruit Fresh and frozen fruit Dried fruit, jelly, jam, canned fruit, sorbets, popsicles

Sweets and sweeteners

Non-caloric sweeteners Sucrose, honey, fructose, glucose, chocolate, candies

Cake, ice creams

Meat and fish Lean and oil fish, poultry without skin

Lean cuts of beef, lamb, pork or veal, seafood, shellfish

Sausages, salami, bacon, spare ribs, hot dogs, organ meats

Dairy food and eggs Skimmed milk and yogurt, egg white

Low fat milk, low fat cheese and other milk products

Regular cheese, cream, egg yolk, whole milk and yoghurt

Cooking fat and dressings

Vinegar, ketchup, mustard, fat-free dressings

Vegetable oils, soft margarines, salad dressing, mayonnaise

Butter, solid margarines, trans fats, palm and coconut oils; lard, bacon fat, dressings made with egg yolks

Nuts/seeds All Coconut

Cooking procedures Grilling, boiling, steaming Stir-frying, roasting Frying


Dietary recommendations to lower

TC and LDL-C


Examples of causes of secondary

hypercholesterolaemia

● Hypothyroidism

● Nephrotic syndrome

● Pregnancy

● Cushing syndrome

● Anorexia nervosa

● Immunosuppressant agents

● Corticosteroids


Recommendations for the pharmacological

treatment of hypercholesterolaemiaRecommendations Class Level

Prescribe statin up to the highest recommended dose, or highest tolerable dose to reach the target level.

I A

In the case of statin intolerance, bile acid sequestrants or nicotinic acid should be considered.

IIa B

A cholesterol absorption inhibitor, alone or in combination with bile acid sequestrants or nicotinic acid, may also be considered in the case of statin intolerance.

IIb C

If target level is not reached, statin combination with a cholesterol absorption inhibitor or bile acid sequestrant or nicotinic acid may be considered.

IIb C


Recommendations for drug treatment of HTG

Recommendations Class Level

In particular high risk patients, lowering of HTG by using the following drugs:

is recommended:fibrates

I B

should be considered:nicotinic acid

IIa B

nicotinic acid + laropiprant IIa C

n-3 fatty acids IIa B

statin + nicotinic acid IIa A

statin + fibrate IIa C

may be considered:combinations with n-3 fatty acids

IIb B


Recommendations if drug treatment of low HDL-C is considered



Nicotinic acid is currently the most efficient drug to raise HDL-C and should be considered.

IIa A

Statins and fibrates raise HDL-C with similar magnitude and these drugs may be considered.

IIb B

The efficacy of fibrates to increase HDL-C may be attenuated in people with type 2 diabetes.

IIb B


Diagnostic criteria for the clinical diagnosis

of HeFH according to MedPed and WHOCriteria Score

Family history

First-degree relative known with premature CAD and/orfirst-degree relative with LDL-C > 95th centile

1

First-degree relative with Tx and/or children < 18 with LDL-C > 95th centile.

2

Clinical historyPatient has premature CAD 2

Patient has premature cerebral/peripheral vascular disease 1

Physical examinationTx 6

Arcus cornealis below the age of 45 years 4

LDL-C

> 8.5 mmol/L (more than ~ 330 mg/dL) 8

6.5-8.4 mmol/L (~ 250-329 mg/dL) 5

5.0-6.4 mmol/L (~ 190-249 mg/dL) 3

4.0-4.9 mmol/L (~ 155-189 mg/dL) 1

Definite FH Score > 8

Probable FH Score 6-8

Possible FH Score 3-5

No diagnosis Score < 3


Recommendations for detection andtreatment of patients with HeFH



FH is suspected in patients with CVD aged < 50 years among men or < 60 years among women, in subjects with relatives with premature CVD or in subjects with known FH in the family.

I C

It is recommended to confirm the diagnosis with clinical criteria or whenever the resources are available with DNA analysis. I C

Family screening is indicated when a patient with HeFH is diagnosed; if resources are available it is recommended to perform this as cascade screening. I C

In HeFH high dose statin is recommended and whenever needed in combination with cholesterol absorption inhibitors and/or a bile acid sequestrant. I C

Children of parents with FH are recommended:• to be diagnosed as early as possible,• to be educated to adopt a proper diet,• to receive pharmacological treatment in late childhood or in adolescence.

I C

Children with HoFH need special attention already from the first year of life. I C

Treatment is aimed at reaching the LDL-C goals for high risk subjects (< 2.5 mmol/L, less than ~ 100 mg/dL) or in the presence of CVD of very high risk subjects (< 1.8 mmol/L, less than ~ 70 mg/dL). If targets cannot be reached, maximal reduction of LDL-C should be considered using appropriate drug combinations in tolerated doses.

IIa C


Genetic disorders of lipoprotein metabolism

Disorder Prevalence Gene(s) Effect on lipoproteins

HeFH I in 500LDLRPCSK9APO B

LDL

HoFH I in 106 LDLR LDL

FCH I in 100/200 USFI + modifying genes LDL, VLD APO B

Familial dysbetalipoproteinaemia I in 5000 APO E IDL and chylomicron remnants (VLDL)

Familial lipoprotein lipase deficiency

I in 106 LPLAPO C2

chylomicronsand VLDL

Tangier disease (analphalipoproteinaemia)

I in 106 ABC-i HDL

Familial LCAT deficiency (fish eye disease)

I in 106 LCAT HDL


Management of dyslipidaemia in women

● Statin treatment is recommended for primary prevention of CAD in high risk women.

● Statins are recommended for secondary prevention in women with the same indications and targets as in men.

● Lipid-lowering drugs should not be given when pregnancy is planned, during pregnancy or during the breast feeding period.


Recommendations for treatment of

dyslipidaemia in the elderlyRecommendations Class Level

Treatment with statins is recommended for elderly patients with established CVD in the same way as for younger patients.

I B

Since elderly people often have comorbidities and have altered pharmacokinetics, it is recommended to start lipid-lowering medication at a low dose and then titrate with caution to achieve target lipid levels which are the same as in the younger subjects.

I C

Statin therapy may be considered in elderly subjects free of CVD, particularly in the presence of at least one other CV risk factor besides age.

IIb B


Summary of dyslipidaemia in MetS

and in type 2 diabetes● Dyslipidaemia in MetS represents a cluster of lipid and lipoprotein

abnormalities including elevation of both fasting and postprandial TGs, apo B, and small dense LDL, and low HDL-C and apo A 1.

● Non-HDL-C or apo B are good surrogate markers of TRLs and remnants and are a secondary objective of theramy.

Non-HDL-C < 3.3 mmol/L (less than ~ 130 mg/dL) or apo B < 100 mg/dL is desirable.

● Increased waist circumference and elevation of TGs seems to be a simple tool to capture the high risk subjects with MetS.

● Atherogenic dyslipidaemia is one of the major risk factors for CVD in people with type 2 diabetes.


Recommendations for treatment of

dyslipidaemia in diabetesRecommendations Class Level

In all patients with type 1 diabetes and in the presence of microalbuminuria and renal disease, LDL-C lowering (at least 30%) with statins as the first choice (eventually drug combination) is recommended irrespective of the basal LDL-C concentration.

I C

In patients with type 2 diabetes and CVD or CKD, and in those without CVD who are over the age of 40 years with one or more other CVD risk factors or markers of target organ damage, the recommended goal for LDL-C is < 1.8 mmol/L (less than ~ 70 mg/dL) and the secondary goal for non-HDL-C is < 2.6 mmol/L (100 mg/dL) and for apo B is < 80 mg/dL.

I B

In all people with type 2 diabetes LDL-C < 2.5 mmol/L (less than ~ 100 mg/dL) is the primary target. Non-HDL-C < 3.3 mmol/L (130 mg/dL) and apo B < 100 mg/dL are the secondary targets.

I B

Ray KK et al. Eur Heart J 2014 Mar 17 [Epub ahead of print]

Comparison of individuals who should be targeted for lipid modification



Tips to help compliance with

multiple drug therapies● Simplify the dosing regimen if possible by reducing daily doses and

concomitant medications.

● Choose cheaper alternatives.

● Provide clear written and oral instructions.

● Undertake a dialogue with the patient regarding adherence.

● Tailor the regimen to the patient’s lifestyle and needs.

● Involve the patient as partner in the treatment.

● Use behavioural strategies (reminder systems, cues, self-monitoring, (feedback, reinforcement).


Percentage reduction of LDL-C requested toachieve goals as a function of the starting value


STARTING LDL-C % REDUCTION TO REACH LDL-C

mmol/L ~ mg/dL< 1.8 mmol/L(~ 70 mg/dL)

< 2.5 mmol/(~ 100 mg/dL)

< 3 mmol/L(~ 115 mg/dL)

> 6.2 > 240 > 70 > 60 > 55

5.2–6.2 200–240 65–70 50–60 40–55

4.4–5.2 170–200 60–65 40–50 30–45

3.9–4.4 150–170 55–60 35–40 25–30

3.4–3.9 130–150 45–55 25–35 10–25

2.9–3.4 110–130 35–45 10–25 < 10

2.3–2.9 90–110 22–35 < 10 –

1.8–2.3 70–90 < 22 – –


A systematic review and meta-analysis on the therapeutic equivalence of

statins

Weng TC, et al. J Clin Pharm Ther. 2010;35;139-151Mukhtar RY, et al. Int J Clin Pract. 2005;59(2):239-252

A10 A20 A40 A80 F20 F40 F80 L20 L40 L80L10 P10 P20 P40 S10 S20 S40 S80 R5 R10 R20 R40 P1 P2 P4

ATOR FLUVA LOVA PRAVA SIMVA ROSU PITA

70

60

50

40

30

20

10

0

LDL %

VOYAGERVOYAGERVOYAGER: an indiVOYAGER: an indiVVidual patient data meta-analysis idual patient data meta-analysis OOf statin f statin

theraptherapYY in in AAt risk t risk GGroups: roups: EEffects of ffects of RRosuvastatin, osuvastatin, atorvastatin and simvastatinatorvastatin and simvastatin

• VOYAGERVOYAGER1 1 is anis an individual patient dataindividual patient data meta-analysis meta-analysis of 32 258 patients from 37 studiesof 32 258 patients from 37 studies– >4 weeks duration>4 weeks duration – fixed-dose comparisons of rosuvastatin with fixed-dose comparisons of rosuvastatin with

atorvastatin or simvastatinatorvastatin or simvastatin– lipid levels recorded at baseline and on therapylipid levels recorded at baseline and on therapy

• Present analysisPresent analysis– data from 30 102 patient exposures to daily data from 30 102 patient exposures to daily

treatment with rosuvastatin 10–40 mg or treatment with rosuvastatin 10–40 mg or atorvastatin 10–80 mgatorvastatin 10–80 mg

– only data from randomised studies directly only data from randomised studies directly comparing treatments were usedcomparing treatments were used

1. Nicholls SJ et al. Am J Cardiol 2010; 105: 69–76.

The VOYAGER population

†Studies involving forced-titration to higher statin doses meant that there was a greater number of ‘exposures’ to individual doses of statins than there were patients within the overall VOYAGER population

Updated: 12 Sept 2012

Whole populationn=32 258

Nicholls SJ et al. Am J Cardiol 2010; 105: 69–76Barter PJ et al. J Lipid Res

2010; 51(6): 1546–53 (HDL-C analysis)(38 199 patient exposures†)

High-risk populationn=21 656

Nicholls SJ et al. Am J Cardiol 2010; 105: 69–76 (26 646 patient exposures†)

Lundman P et al. Atheroscler Suppl 2011; 12: 164 (abstract) (5741 patient exposures†)

Diabetes n=8859Karlson BW et al. Nut Metab Cardiovasc Dis

2012; 22: 697–703(11 042 patient exposures†)

Age Nicholls S et al. Atheroscler Suppl

2010; 11: 119 (abstract)(34 041 patient exposures†)

21% of patients ≥70 y

Gender Lundman P et al. Atheroscler Suppl

2010; 11: 75 (abstract) (34 038 patient exposures†)

43% of patients female

Atherosclerotic disease n=15 498Nicholls S et al. Atheroscler Suppl

2009; 10: 964 (abstract) (19 437 patient exposures†)

LDL-C goal achievementKarlson B et al. Eur Heart J

(Suppl) 2011; 32: 342 (abstract) (30 102 patient exposures†)

Atherogenic dyslipidaemia n=6061 (7673 patient exposures†) Lipid ratios

Nicholls S et al. Eur Heart J (Suppl 1) 2010; 31: 391 (abstract)

Karlson BW et al. European Atherosclerosis Society Congress, May 2012 (abstract 170)

High-risk high baseline LDL-CLundman P et al. Atheroscler Suppl

2011; 12: 164 (abstract) (5741 patient exposures†)

Achievement of 2011 Eu LDL-C goalsKarlson BW et al. Int Symposium Atheroscler

March 2012; (abstract 181) Karlson BW et al. European Atherosclerosis Society

Congress, May 2012; (abstract 409)(25 075 patient exposures†)

hsCRP analysisNicholls SJ et al. European Atherosclerosis Society Congress, May 2012 (abstract 432)

(6413 patient exposures† with baseline hsCRP recorded)

Change in LDL-C Levels with Increasing Change in LDL-C Levels with Increasing Dose of Each Statin: Dose of Each Statin:

VOYAGER Whole PopulationVOYAGER Whole Population

Adapted by permission from Elsevier Inc.

Ch

an

ge in

LD

L-C

fro

m

baselin

e (

%)

Dose (log scale)5 mg 10 mg 20 mg 40 mg 80 mg

-27(n=365)

-33 (n=2929)

-39 (n=548) -45

(n=479)

-50##

(n=2072) -55‡

(n=2983)

-50† (n=3554)

-44* (n=11 690)

-39 (n=670)

-36 (n= 7837)

-41#

(n=3908)-46

(n=1324)

*p<0.001 rosuvastatin 10 mg vs atorvastatin 10 mg and 20 mg; simvastatin 10 mg, 20 mg and 40 mg †p<0.001 rosuvastatin 20 mg vs atorvastatin 20 mg and 40 mg; simvastatin 20 mg ,40 mg and 80mg ‡p<0.001 rosuvastatin 40 mg vs atorvastatin 40 mg and 80 mg; simvastatin 40 mg and 80 mg#p<0.05 atorvastatin 20 mg vs rosuvastatin 5 mg ##p<0.05 atorvastatin 80 mg vs rosuvastatin 5 mg and 10 mg

Nicholls SJ et al. Am J Cardiol 2010; 105: 69–76

Percentage of patients achieving treatment Percentage of patients achieving treatment goal LDL-C <100 mg/dLgoal LDL-C <100 mg/dL

Rosuvastatin 20 mg versus atorvastatin 20 mgRosuvastatin 20 mg versus atorvastatin 20 mg

9 direct comparison studiesComparison of fitted curves: odds ratio = 2.92, p<0.001

Baseline LDL-C, mg/dL (mmol/L)

120 140 160 180 200 220

0

20

40

60

80

100

% p

ati

en

ts a

ch

ievin

g L

DL-C

<

10

0 m

g/d

L (

2.6

mm

ol/

L)

Rosuvastatin 20 mg (n=2017)

Atorvastatin 20 mg (n=1910)

(3.1) (3.6) (4.1) (4.7) (5.2) (5.7) (6.2)240

Percentage of patients achieving treatment Percentage of patients achieving treatment goal LDL-C <100 mg/dLgoal LDL-C <100 mg/dL

Rosuvastatin 20 mg versus atorvastatin 40 mgRosuvastatin 20 mg versus atorvastatin 40 mg

5 direct comparison studiesComparison of fitted curves: odds ratio = 1.93, p<0.001

120 140 160 180 200 220 240

0

20

40

60

80

100

% p

ati

en

ts a

ch

ievin

g L

DL-C

<

10

0 m

g/d

L (

2.6

mm

ol/

L)

Rosuvastatin 20 mg (n=628)

Atorvastatin 40 mg (n=624)

Baseline LDL-C, mg/dL (mmol/L)(3.1) (3.6) (4.1) (4.7) (5.2) (5.7) (6.2)

High-risk patients achieving the new High-risk patients achieving the new

European LDL-C goal European LDL-C goal

(LDL-C <70 mg/dL or >50% reduction) (LDL-C <70 mg/dL or >50% reduction)

100

80

60

40

20

0

Pati

en

ts a

t g

oal (%

)

2010 40 80Statin dose (mg)

Rosuvastatin Atorvastatin

n=7583

n=2246

n=1990

n=5226

n=2818

n=898

n=1554

Simvastatin

n=174

n=428

n=2099n=59

RR

RRRR

RR

SS

AA

AA

AA

AA

AA

SS

SS

SS

SS

CONTROLLED CLINICAL TRIALS

PROVIDE HIGH QUALITY DATA BUT

• Exclude specific subgroups of patients

• Exclude concomitant unwanted treatments

• Adhesion and compliance are at high level

Relation between proportional reduction in incidence

of major coronary events and major vascular events and mean absolute LDL cholesterol

reduction at 1 year

Cholesterol Treatment Trialists’ (CTT) Collaborators Lancet 2005;366:1267-78

REAL LIFE

• Less selected patients

• Coadministration of potentially interfering drugs

• Adherence and persistence less than optimal

IS THERE A PRICE TO PAY?

WHO describes poor adherence as a worldwide problem with striking magnitude

Poor adherence itself is a problem which should be viewed as diagnosable and treatable !

JAMA 2013;309:2105

WHO describes poor adherence as a worldwide problem with striking magnitude

Poor adherence itself is a problem which should be viewed as diagnosable and treatable !

JAMA 2013;309:2105

Chowdhury et al., EHJ 2013;34:2940–8

Prevalence of good adherence (>80%) to CV medications

among participants in prospective studiesMeta-analysis of 44 studies, n= 1 978 919; 135 627 CVD events; 94 126 cases of all-cause

mortality

40%poor adherence

WHAT HAPPENS THEN?

Statin Under-dosing is associated with an Adverse Outcome

Rasmussen et al., JAMA. 2007 Jan; 297(2):177-186 Rasmussen et al., JAMA. 2007 Jan; 297(2):177-186

Shalev V, et al. Arch Intern Med 2009; 169:260-268

Proportion of Days Covered With Statins and All-Cause Mortality, Maccabi Healthcare Services, Israel, 1998-2006

Risk of IHD (Hospital Diagnosis) in Patients Treated with Statin Risk of IHD (Hospital Diagnosis) in Patients Treated with Statin (n = 190.877)(n = 190.877)

Risk of IHD (Hospital Diagnosis) in Patients Treated with Statin Risk of IHD (Hospital Diagnosis) in Patients Treated with Statin (n = 190.877)(n = 190.877)

Catapano, et al., in preparationCatapano, et al., in preparation

Months with Months with

drug availabledrug available

< 6< 6

7-127-12

13-2413-24

25-3625-36

≥ ≥ 3636

HR (95% CI)HR (95% CI)

0.97 (0.79-1.18)0.97 (0.79-1.18)

0.87 (0.73-1.03)0.87 (0.73-1.03)

0.75 (0.62-0.91)0.75 (0.62-0.91)

0.75 (0.59-0.94)0.75 (0.59-0.94)

0.50.5 1.01.0 2.02.0

HRHR

P for trend P for trend = 0.0007= 0.0007

Corrao G et al. Atherosclerosis 2014;234:224-9

Flow chart of inclusion and exclusion criteria


Characteristics of the 458 case patients hospitalized for acute

kidney injury and of the corresponding

1824 controls included into the study


Association between the statin type

employed at treatment initiation (upper panel) and during the current

time-window (lower panel) and the risk of

hospitalization for acute kidney injury

Odds ratios, and corresponding 95% confidence intervals, of acute kidney injury associated with dispensing: (upper panel) high vs. low-potency statin at treatment initiation (lower panel) high and low-potency statin during the current time-window, vs. any statin dispensation during the same period. Estimates are unadjusted (crude) and adjusted for use of other drugs, hospitalization for heart failure, and Charlson comorbidity index score


Effect of acute exposure to high-potency statin on the onset of acute kidney injury during the first six months after therapy

starting (main analysis), the onset of acute kidney injury during the first twelve months after therapy starting, and the onset of chronic kidney injury within six months after starting therapy


Jesus Millan Nuñez-Cortes

Juan Pedro-Botet Montoya

Chair Co-Chair

the esc/eas guidelines

Health & Medicine

hdl hdl

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levels of risk

risk factors

risk function

risk estimates

terms of risk

risk assessment