Dyslipidemia in the light of Current Guidelines - Do we change our Practice?

Transcription

1 Dyslipidemia in the light of Current Guidelines - Do we change our Practice? Dato Dr. David Chew Soon Ping Senior Consultant Cardiologist Institut Jantung Negara

2 Atherosclerotic Cardiovascular Disease Most important cause of premature mortality and disability Include coronary artery disease, ischaemic stroke and peripheral vascular disease

3 CV risk factors Non modifiable: age, sex, family history Modifiable: dyslipidemia, hypertension, smoking, diabetes, abdominal obesity, psychosocial stress, diet (low fruit and vegetable intake), physical inactivity

4 Reducing Cardiovascular Risk Global cardiovascular risk estimation Primary prevention of cardiovascular disease and secondary prevention of cardiovascular events: Control of CV risk factors by lifestyle modification and drug therapy

5 Therapeutic Lifestyle Changes Cardioprotective diet: low in fat, saturated fat, cholesterol; more fruits and vegetables Physical activity Weight management Smoking cessation

6 Dyslipidemia Elevated LDL cholesterol linked to development of atherosclerotic vascular disease Drug therapy with statins reduce LDL cholesterol effectively and has been shown to reduce CV risk and CV events

7 Primary Prevention Trials Patients at risk: hypertension, diabetes, hscrp > 2 mg/l LDL cholesterol from mmol/l Use of statins (pravastatin, lovastatin, atorvastin, rosuvastatin) vs placebo

8 Primary prevention

9 Secondary Prevention Trials Patients with CHD, peripheral vascular disease, stroke-transient ischemic attack, or diabetes LDL cholesterol from 5.0 to 2.8 mmol/l Use of statins (simvastatin, pravastatin) vs placebo

10 Secondary prevention

11 Intensive LDL cholesterol lowering In patients with ACS, post MI or stable CAD Comparing high dose statin (atorvastatin 80 mg, simvastatin 80 mg) vs low dose statin (pravastatin 40 mg, simvastatin 20 mg, atorvastatin 10 mg)

12 Individual trials and pooled analysis showing a 16% reduction in the risk of coronary death or myocardial infarction Study Odds reduction (%) Event rates, n/total (%), high dose Event rates, n/total (%), standard dose PROVE IT-TIMI /2099 (7.0) 172/2063 (8.3) A to Z /2265 (9.1) 235/2232 (10.5) TNT /4995 (6.7) 418/5006 (8.3) IDEAL /4439 (9.3) 463/4449 (10.4) Total /13798 (8.0) 1288/13750 (9.4) Cannon CP et al. J Am Coll Cardiol 2006; 48:

13 Relationship between LDL Cholesterol and CV events in patients with existing CHD

14 Three Categories of Risk that Modify LDL-Cholesterol Goals Risk Category LDL Goal (mmol/l) CHD and CHD risk equivalents (2 nd ) Multiple (2+) risk factors (1 prevention) Zero to one risk factor <2.6 (1.8) <3.4 <4.1

15 2013 ACC AHA Guideline

16 2013 ACC AHA guidelines Treatment of cholesterol levels to reduce atherosclerotic cardiovascular disease (coronary artery disease, stroke and peripheral arterial disease) risk Is the patient s ASCVD risk high enough to merit treatment with statins (rather than whether LDL-C is high enough to justify treatment)?

17 Data from RCTs and Meta-analysis Various strategies for using drug therapy to reduce ASCVD events: treat-to-cholesterol target, lower cholesterol is better, and riskbased treatment approaches. Only 1 approach has been evaluated in multiple RCTs the use of fixed doses of cholesterol-lowering drugs to reduce ASCVD risk

18 Why statin Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial showed that torcetrapib, which lowered LDL levels by about 25%, increased the risk of death. Ezetimibe effectively reduces LDL but has not been shown to improve patient outcomes

19 Focus on ASCVD Risk Reduction: 4 statin benefit groups* Clinical ASCVD LDL-C level 190 mg/dl (4.9 mmol/l) Diabetes, aged years, with LDL-C of mg/dl ( mmol/l) Estimated 10-year risk of ASCVD of 7.5%, years of age, and with LDL-C mg/dl ( mmol/l) * Moderate- or high-intensity statin therapy recommended for these 4 groups Clinical ASCVD defined as acute Cardiovascular coronary syndromes, Updates for history Doctors of MI, & Allied stable Healthcare or unstable Professionals angina, coronary Symposium or arterial revascularization, stroke, transient ischemic attacks, or peripheral artery disease Estimated using Pooled Cohort Risk Assessment Equations

20 High, Moderate and Low Intensity Statin Therapy High-Intensity Statin Therapy Moderate-Intensity Stain Therapy Low-Intensity Statin Therapy LDL C 50% LDL C 30% to <50% LDL C <30% Atorvastatin (40 ) 80 mg Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2 4 mg Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg Lifestyle modification remains a critical component of ASCVD risk reduction, both prior to and in concert with the use of cholesterol lowering drug therapies. Statins/doses that were not tested in randomized controlled trials (RCTs) reviewed are listed in italics Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL Initiation of or titration to simvastatin 80 mg not recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis.

21 Secondary Prevention Clinical ASCVD and 75 years old High-Intensity Statin Moderate-intensity statin therapy is recommended for patients with clinical ASCVD age >75 years, or in those patients who are not candidates for high-intensity statin therapy due to safety or tolerability considerations.

22 Primary Prevention Patients 21 years old with LDL-C 190 mg/dl High-Intensity Statin If high-intensity statin not tolerated, use maximum tolerated statin intensity After maximum statin intensity has been achieved, addition of a non-statin drug to further lower LDL-C may be considered Stone NJ, et al. J Am Coll Cardiol. 2013: doi: /j.jacc Available at: Accessed November 13, 2013.

23 Primary Prevention Moderate-Intensity Statin Patients with Diabetes and LDL-C mg/dl (age years) without clinical ASCVD High-Intensity Statin if 7.5% estimated 10-year ASCVD risk* * Estimated using Pooled Cohort Cardiovascular Risk Assessment Updates Equations for Doctors & Allied Healthcare Professionals Symposium Stone NJ, et al. J Am Coll Cardiol. 2013: doi: /j.jacc Available at: Accessed November 13, 2013.

24 Primary Prevention Patients with LDL-C mg/dl without diabetes and without clinical ASCVD Estimated 10 year ASCVD risk 7.5%* Yes Moderate- to high-intensity statin therapy No Consider additional factors to inform treatment decision * Estimated using the Pooled Cohort Risk Assessment Equations

25 Additional factors to consider LDL C 160 mg/dl (4.1 mmol.l) or evidence of genetic hyperlipidemias Family history of premature ASCVD in males <55 years of age or females <65 years of age Hs C-reactive protein >2 mg/l CAC score 300 Agatston units or 75 percentile for age, sex, and ethnicity Ankle-brachial index <0.9 Elevated lifetime risk of ASCVD

26 Pooled Cohort Equation Combined Framingham with ARIC, Cardiovascular Health Study and CARDIA (Coronary Artery Risk Development In young Adults) cohorts Risk of CHD death, non fatal MI, fatal and non fatal stroke Variables: age, total and HDL-cholesterol, systolic Cardiovascular BP (including Updates for Doctors & Allied treated Healthcare Professionals or untreated Symposium status), diabetes, and current smoking status

27 Risk calculator at

28 Disadvantages of Pooled Risk score Other risk factors not taken into account No trials have used the risk score to identify patients for inclusion Pooled cohort equation may overestimate risk (when applied in 3 primary prevention cohorts: Women Health study, Physician Health study & Women s health observational Study; risk overestimated by %)

29 Adverse effects of statins Risk of diabetes: For every 255 patients treated for 4 years, there may be 1 new case of DM, but 5.4 CV events will be prevented moderate-intensity statins, 0.1 excess case of diabetes /100 statin-treated individuals / year high intensity statin, 0.3 excess cases of diabetes /100 statin-treated individuals / year Myopathy (~0.01 excess case per 100 pts/year) and hemorrhagic stroke (~0.01 excess case per 100 pts/year)

30 Implications of New Guidelines Avoidance of cholesterol lowering therapy in certain patient groups (on HD, heart failure) Avoidance of non statin LDL cholesterol lowering agents in statin tolerant patients Use of a new risk calculator that target larger numbers of patients for statin treatment.

31 US Adults who would be eligible for statin therapy for primary prevention

32 Conclusion 1 Lifestyle changes are still important Risk assessment is important for patients without ASCVD Pooled equation Framingham Discussion of risk benefits with patients

33 Framingham Risk Score 2008 Risk of MI and CHD death

34 Conclusion 2 Focus on statin evidence based. High intensity for high risk Less emphasis on non-statin drug therapy Shift away from a target LDL-C approach but should still monitor levels (compliance & possibly better)

35 CHD events by achieved LDL Cholesterol levels PROVE IT

36 Other Lipid Lowering Drugs Ezetimibe: inhibits exogenous cholesterol absorption Fibrates: reduce TG and may increase HDL Niacin & fish oils