2013 ACC AHA LIPID GUIDELINE JAY S. FONTE, MD

Transcription

1 2013 ACC AHA LIPID GUIDELINE JAY S. FONTE, MD

2 How do you interpret my blood test results? What are our targets for these tests?

3 Before the ACC/AHA Lipid Guidelines A1c: <7% BP: <140/90 Cholesterol (LDL) Primary Prevention: < 100mg/dl Secondary Prevention: <70 mg/dl

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5 Reviewing the evidence for LDL-C goals RCTs used fixed-dose statin therapy to lower LDL-C levels statin vs. placebo (4S) high vs. low dose statin (TNT)

6 CTT: Effect on MAJOR VASCULAR EVENTS per mmol/l LDL-C reduction in more vs less intensive statin regimen No. of events (% pa) More statin Less statin Relative risk (CI) per mmol/l LDL-C reduction Nonfatal MI 1175 (1.3%) 1380 (1.5%) 0.71 ( ) CHD death Any major coronary event 645 (0.7%) 1725 (1.9%) 694 (0.7%) 1973 (2.2%) 0.85 ( ) 0.74 ( ) CABG 637 (0.7%) 731 (0.9%) 0.72 ( ) PTCA Unspecified 1166 (1.3%) 447 (0.5%) 1508 (1.8%) 502 (0.6%) 0.60 ( ) 0.78 ( ) Any coronary revascularisation 2250 (2.6%) 2741 (3.2%) 0.66 ( ) Ischaemic stroke Haemorrhagic stroke 440 (0.5%) 69 (0.1%) 526 (0.6%) 57 (0.1%) 0.69 ( ) 1.39 ( ) Unknown stroke Any stroke 63 (0.1%) 572 (0.6%) 80 (0.1%) 663 (0.7%) 0.63 ( ) 0.74 ( ) Any major vascular event 3837 (4.5%) 4416 (5.3%) 0.72 ( ) 99% or 95% CI More statin better Less statin better CTT Collaboration. Lancet 2010; 376:

7 Reviewing the evidence for LDL-C goals There was no RCT comparing the outcome of targeting LDL-C targets of <100 mg/dl or <70mg/dL for very high risk and high risk patients, respectively. The Lower, the better! Event Reduction is Independent of Baseline LDL-C Non-HDL Cholesterol = Total Cholesterol HDL cholesterol

8 CTT: Effect on Major Vascular Events LOWER IS BETTER Proportional reduction in event rate 30% 25% 20% 15% 10% 5% More vs Less (5 trials) Statin vs control (21 trials) 1 mmol/l (~39 mg/dl) reduction 20% reduction in risk 2-3 mmol/l reduction 40-50% reduction in risk 0% Mean LDL cholesterol difference between treatment groups (mg/dl) CTT Collaboration. Lancet 2010; 376:

9 Individuals with the highest baseline risk will benefit more from Statin treatment Baseline risk (risk of CV event over five years), % Risk reduction (95% CI) per 1-mmol LDL reduction < ( ) ( ) ( ) ( ) ( ) Overall 0.76 ( ) Cholesterol Treatment Trialists (CTT) Collaborators Published online May 17, 2012

10 Implications of treating to an LDL-C and non-hdl-c goal using NCEP ATP III 56 yrs old male, T2 DM, no comorbidities, LDL-C: 111mg/dl Target by NCEP ATP III: <100mg/dl Rx: low dose statin

11 Implications of treating to an LDL-C and non-hdl-c goal using NCEP ATP III 56 yrs old male, T2 DM, LDL-C: 99 mg/dl (on low intensity Statin); Triglycerides: 210 mg/dl; HDL: 40 mg/dl; Total Cholesterol: 203 mg/dl Rx: low dose statin fibrates

12 Guidelines identify four statin benefit groups Group 1 Clinical ASCVD CHD, stroke, and peripheral arterial disease, all of presumed atherosclerotic origin Group 2 LDL-C 190 mg/dl (~5 mmol/l) ASCVD, atherosclerotic cardiovascular disease CHD, coronary 12 heart disease LDL-C, low density lipoprotein-cholesterol Group 3 DM + age of years + LDL-C mg/dl (~1.8 5 mmol/l) Group 4 ASCVD risk 7.5% No diabetes + age of years + LDL-C mg/dl (~1.8 5 mmol/l) Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print

13 ACC AHA Lipid Guideline for Individuals with Diabetes Mellitus Type 1 or 2 diabetes Age years Yes No Consider statin for individual patients Estimate 10-year ASCVD risk with Pooled Cohort Equations ASCVD risk 7.5% ASCVD risk <7.5% High-intensity statin* Moderate-intensity statin *Expected 13 to reduce LDL-C by 50% Expected to reduce LDL-C by 30 to <50% Stone NJ, et al. J Am Coll Cardiol 2013 Nov

14 Risk factor Guidelines use new ASCVD risk calculator Sex (male or female) Age (years) Race (African-American or White/other) Total cholesterol (mg/dl) HDL-C (mg/dl) SBP (mmhg) Treatment for high BP (yes or no) Diabetes (yes or no) Smoker (yes or no) 10-year risk (%) of ASCVD (non-fatal MI, CHD death, or fatal/non-fatal stroke) is calculated from simple parameters: BP, blood pressure HDL-C, high 14 density lipoprotein-cholesterol SBP, Systolic blood pressure Goff DC Jr, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print

15 Intensity of Statin Therapy High Moderate Low ê LDL-C 50% ê LDL-C 30 to <50% ê LDL-C <30% Atorva mg Rosuva mg Atorva 10 mg Rosuva 10 mg Simva mg Pravas 40 mg Lova 40 mg Fluva XL 80 mg Fluva 40 mg bid Pitava 2-4 mg Statins in bold were evaluated in randomized controlled trials; those in italics were not Simva 10 mg Prava mg Lova 20 mg Fluva mg Pitava 1 mg 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, p 34

16 How do we address mixed dyslipidemia in individuals with diabetes? Normal LDL-C, elevated small dense LDL High Triglycerides Low HDL-C

17 Combination Therapy in Patients with Diabetes Niacin = AIM HIGH Trial Fenofibrate = ACCORD Lipid Trial Ezetimibe = IMPROVE IT Bile acid sequestrants There is insufficient evidence that such combination therapy provides a significant increment in CVD risk reduction over statin therapy alone

18 Lipid Abnormality in Diabetes Elevated small dense LDL Elevated Triglycerides Low HDL-C

19 Implications of ACC/AHA Lipid Guidelines The number of DM patients who will receive a statin using the ACC/AHA guideline will not significantly change. Patients will receive moderate to high dose statin à More side effects à Very low LDL-C for patients with low baseline LDL-C

20 High-Dose Statin Therapy Associated with an Increased Risk for Statin-Induced Adverse Events AEs OR 95% CI P OR and 95% CI Any AE <0.001 Any AE requiring statin discontinuation <0.001 AST/ALT >3x ULN <0.001 CK >10x ULN Rhabdomyolysis Overall < Intensive dose better Moderate dose better Silva M et al. Clin Ther 2007;29:

21 Recommendations for optimizing statin safety Creatine kinase should not be routinely measured Muscle symptoms: discontinue statin - Unexplained, severe: address possibility of rhabdomyolysis - Mild to moderate: evaluate cause; reinstate statin where appropriate Measure baseline hepatic transaminase levels before initiation - Measure hepatic function if symptoms suggest hepatotoxicity during treatment Consider statin dose if two consecutive LDL-C values <40 mg/dl (~1 mmol/l) Confusional state or memory impairment: evaluate non-statin causes together with possible adverse effects of statins Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print

22 Implications of ACC/AHA Lipid Guidelines There is no specific LDL-C target. Lipid profile may be requested to assess compliance, but may not be needed once the patient is stable on therapy

23 Non-statin therapy is limited only to individuals with insufficient response to statin therapy Non-statin therapy is not recommended for routine therapy Insufficient response to high-intensity statin (LDL-C reduction <50%) Insufficient response to moderate-intensity statin (LDL-C reduction <30%) Re-emphasize adherence to healthy lifestyle and statin statin dose (if needed) Consider addition of non-statin cholesterol-lowering drug(s) Preferably drug shown to ASCVD in RCTs And if benefit of ASCVD outweighs the potential AEs Consider non-statin monotherapy only if patient is completely statin-intolerant Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print

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25 Guidelines for patients with diabetes: ACC/AHA vs ADA ACC/AHA 1 ADA 2 Patient groups Clinical ASCVD: high-intensity statin* Age years, LDL-C mg/dl 10-year ASCVD risk 7.5%: high-intensity statin * 10-year ASCVD risk <7.5%: moderate-intensity statin Age <40 or >75 years: Consider statin individually CVD: LDL-C <1.8 mmol/l (<~70 mg/dl) No CVD, >40 years + 1 other risk factor: LDL-C <2.6 mmol/l (<~100 mg/dl) LDL-C by 30 40% acceptable if target not reached Lower risk: consider statin if LDL-C >100 mg/dl (~2.6 mmol/l) after lifestyle adjustment First-line drug Highest tolerated statin Statin Combination with non-statin If target not reached with highest tolerated statin Not generally recommended (no additional CV benefit) Non-statin drugs alone * Expected to reduce LDL-C by 50% Expected to reduce LDL-C by 30 to <50% ǂ Lower level 25 of evidence than statins ADA, American Diabetes Association If statin not tolerated Fibrate, niacin or fish oil for severe hypertriglyceridemia ǂ 1. Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print; 2. American Diabetes Association Diabetes Care 2013;36(Suppl. 1):S11 S36

26 Guideline comparison: ACC/AHA vs NCEP ATP III Diabetes years First-line drug Combination with nonstatin Non-statin drugs ACC/AHA 1 NCEP ATP III 2,3 10-year ASCVD risk: 7.5%: high-intensity statin * <7.5%: moderateintensity statin Highest tolerated statin If target not reached with highest tolerated statin If statin not tolerated LDL-C <100 mg/dl (~2.5 mmol/ L); <70 mg/dl (~1.8 mmol/l) optional (intensity that LDL-C by 30 40%) Statin usual (LDL-C primary target) Consider adding fibrate or niacin to triglycerides or HDL-C Alternative initial drugs: bile acid sequestrant or niacin *Expected to reduce LDL-C by 50% Expected to reduce LDL-C by 30 to <50% ǂ LDL-C <70 26 mg/dl (< 1.8 mmol/l) optional for patients at highest risk NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III 1. Stone NJ, et al.j Am Coll Cardiol 2013 Nov 7. Epub ahead of print; 2. NCEP Adult Treatment Panel III. Circulation 2002;106: ; 3. Grundy S et al. Circulation 2004;110: