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Common Questions in Lipids 2010

Common Questions in Lipids 2010. Mehul Bhatt, MD Athens Heart Center. Contemporary Guidelines (simple enough). National Cholesterol Education Program (NCEP) 2004 LDL < 70-100 mg/ dL for CAD and CAD-equivalent risk factors < 100-130 mg/ dL for 2+ CAD risk factors

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Common Questions in Lipids 2010

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  1. Common Questions in Lipids 2010 Mehul Bhatt, MD Athens Heart Center

  2. Contemporary Guidelines(simple enough) National Cholesterol Education Program (NCEP) 2004 • LDL • < 70-100 mg/dL for CAD and CAD-equivalent risk factors • < 100-130 mg/dL for 2+ CAD risk factors • < 160 mg/dL for 0-1 CAD risk factor • HDL • > 40 mg/dL • Triglycerides • < 200 mg/dL

  3. Contemporary Guidelines(simple enough) • First: treat LDL . . . • Second: HDL > 40 . . . • Third: Triglyceride < 200

  4. But…what are common lipid questions in 2010? • NCEP guidelines lag behind contemporary lipidology • Common issues: • Best statin • Coenzyme Q-10 • Niacin • Ezetimibe • Nutritional supplements

  5. What is the best statin? • 6 statins available • 3 name-brand: atorvastatin (Lipitor™), fluvastatin (Lescol™), rosuvastatin (Crestor™) • 3 generic: lovastatin (Mevacor™), pravastatin (Pravachol™), simvastatin (Zocor™) • Efficacy of statins in reducing LDL and CV events undisputed • Few head-to-head statin trials

  6. What is the best statin? • Potency • Reduction in LDL at lower dose • Achieve goal LDL < 70-100 • Linear decreasing LDL at higher dosages • Rosuvastatin> Atorvastatin, Simvastatin> Fluvastatin, Lovastatin, Pravastatin From Cannon et al. NEJM 2001

  7. What is the best statin? • Best data in prevention of clinical events: • Pravastatin • Simvastatin • Atorvastatin • Superior to low dose pravastatin • MIRACL, PROVE-IT: improved clinical outcomes in the highest risk patients (during acute coronary syndromes) • Rosuvastatin • JUPITER: improved clinical outcome in low-risk patients with elevated CRP

  8. What is the best statin? • Prevention of cardiovascular events: JUPITER: Rosuvastatin prevents cardiovascular events in low risk patients PROVE-IT TIMI 22: Atovastatin superior to pravastatin after acute coronary syndromes From Cannon et al. NEJM 2001 and Ridker et al. NEJM 2008

  9. What is the best statin? • Atherosclerotic plaque stabilization/regression: • REVERSAL Trial 2004 (atorvastatin) • ASTERIOD Trial 2006 (rosuvastatin) From Nissen et al. JAMA 2004

  10. What is the best statin? • Pleotropic effects • Anti-inflammatory effects in atherosclerotic plaque • Anti-thrombotic • Improve endothelial function • Increasing nitric oxide (vasodilator) • Inhibits endothelin-1 (vasoconstrictor) • Most data with high-dose atorvastatin and rosuvastatin • Perhaps mediated through CRP and/or sCD40

  11. What is the best statin? • Pleotropic effects: • High-dose atorvastatin and rosuvastatin have most proven effect on CRP in large trials From Ridker et al. NEJM 2005

  12. What is the best statin? • Summary: • Benefits of statins undisputed • More benefits in higher risk patients • Acute coronary syndromes, high-CRP, multiple risk factors. . . • Atorvastatin and Rosuvastatin: • Most recent large trials • Atherosclerotic plaque stabilization/regression data • Are they better than less expensive alternatives? • Or do they have more recent data?

  13. Does Coenzyme-Q10 work? • CoQ10 = Ubiquinone • CoQ10: Fat-soluble compound found in hydrophobic portion of mitochondrial membrane • Approx. 10% rate of statin related myalgia • Statins reduce Co-Q10 levels 25-40% • Depletion of skeletal muscle mitochondrial Co-Q10 may lead to myalgia and myopathy From Marcoff et al. JACC 2007

  14. Does Coenzyme-Q10 work? • Co-Q10 supplementation increases plasma level in patient taking statins • Multiple observational and anecdotal reports of improvement in myalgia with Co-Q10 • 2 small randomized trials in patients with history of myalgia did show benefit • Overall, Co-Q10 harmless, inexpensive, and may reduce statin-related myalgia

  15. Niacin, revisited… • Niacin used clinically in heart disease for over 50 years (pre-statin era) • 1st randomized controlled trial in lipids in CAD: • Coronary Drug Project: Clofibrate and niacin in coronary heart disease. JAMA 1975; • 8,341 males from 31-64 years old with history of MI • Randomized to conjugated estrogens, clofibrate, dextrothyroxine, niacin (3000 mg/day), or placebo • Niacin had early reduction in rates of MI and a mortality benefit that was maintained at 15-year follow-up! From JAMA 1975 and Canner et al. JACC 1986

  16. Niacin, revisited… • Niacin = Nicotinic acid = Vitamin B3 • In high doses decreases LDL, increases HDL • Most common side effects are flushing, itching, rash • Over-the-counter; relatively inexpensive • Niacin extended-release tablets: available since 1997 (Niaspan) does reduce flushing rates • NSAIDs 30 min before niacin and extended-release niacin are shown to reduce flushing

  17. Niacin, revisited… ARBITER 6-HALTS • CAD patients with LDL < 100, HDL < 50-55 • statin + extended-release niacin (2000 mg/day) - versus - statin + ezetimibe • Lower LDL with ezetimibe • Higher HDL and lower TG with niacin • BUT OUTCOMES. . . From Taylor et al. NEJM 2009

  18. Is there any value to ezetimibe? • Ezetimibe (Zetia) • Decreases intestinal absorption of cholesterol • Effective in reducing LDL • But, does not reduce plaque or clinical event • Probably only useful when statins not toleratated

  19. Nutritional supplement therapy

  20. Summary • Treat CAD and CAD-equivalent patients to LDL goal < 70-100 • “Best statin”: atorvastatin and rosuvastatin have most recent data with pleotrophic effects and plaque stabilization/regression • Niacin has important role in lipid management • Some quality nutritional supplement have value www.athensheartcenter.com

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