Niacin and Coronary Heart Disease
Niacin and Coronary Heart Disease
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman serves on the speakers bureau for Forest Laboratories.
Synopsis: Among patients with coronary heart disease and LDL-cholesterol levels less than 70 mg/dL, there is no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up, despite improvements in HDL-cholesterol and triglyceride levels.
Source: The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365:2255-2267.
Elevated low-density lipoprotein (LDL) cholesterol levels are established predictors for the risk of developing coronary heart disease (CHD), and, despite the fact that multiple primary and secondary prevention trials have shown a 25%-35% CHD risk reduction in patients receiving statin therapy,1 a significant residual CHD risk persists even if target LDL cholesterol levels are achieved. Epidemiologic studies have demonstrated that in addition to elevated LDL cholesterol levels, low levels of high-density lipoprotein (HDL) cholesterol are an independent predictor of the risk of CHD with a strong inverse association between HDL cholesterol levels and the rates of incidents CHD events.2,3
Aggressive lowering of lipid levels with high doses of statins to achieve a target LDL cholesterol level less than 70 mg/dL in very high-risk patients has resulted in major reductions in clinical endpoints. Treatment with simvastatin plus niacin has also resulted in significant regression of angiographic coronary atherosclerosis and reductions in the rate of clinical events.4,5 The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) investigators prospectively studied 3414 patients who were being treated with simvastatin and randomly assigned them to receive either niacin or placebo. They determined that among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels less than 70 mg/dL, there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up, despite significant improvement in HDL cholesterol and triglyceride levels.6
Commentary
Currently, no one questions the cardiovascular benefits of target LDL-cholesterol reduction to less than 100 mg/dL and even to less than 70 mg/dL in high-risk patients. Also, continuing evolutions in medical therapy over the past several decades with the development of other disease modifying interventions, such as antiplatelet therapy and now beta-blocker and renin-angiotensin system inhibitors, are recommended for all patients who have had a myocardial infarction (MI) to improve outcomes and reduce the incidence of recurrent MIs.6 Raising HDL cholesterol levels has proven to be beneficial,7,8 but the residual question has been whether there is a true benefit in raising the HDL cholesterol level in persons who have received effective statin therapy. The AIM-HIGH trial was designed to evaluate the possible benefit of adding niacin to statin therapy as compared to statin therapy with or without ezetamide but without niacin. The investigators were attempting to determine if a further decrease in the incidence of major cardiac events occurred among subjects with CHD who had residual dyslipidemia and low levels of HDL cholesterol at baseline but who have met a treatment goal by achieving an LDL cholesterol level of 40-70 mg/dL with statin therapy. It would appear from the results of the study that patients whose LDL cholesterol levels were intensively controlled with simvastatin therapy received no incremental benefit from niacin in reducing the cardiovascular events which occurred over a 36-month follow-up period, despite significant increases in HDL cholesterol and decreases in triglyceride levels.
In summary, it would appear that the primary goal of clinicians should be to lower the LDL cholesterol to at least 70 mg/dL (although 50-60 mg/dL may be even better). Statin therapy and niacin therapy appear to be of little or no value in this group of patients regardless of its positive effects on the HDL cholesterol and triglyceride levels. Further studies will be required to determine whether the raising of HDL cholesterol levels in subjects whose LDL levels are not so intensely controlled will be of added value.
References
1. Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376: 1670-1681.
2. Castelli WP, et al. Cholesterol and lipids in the risk of coronary artery disease the Framingham Heart Study. Can J Cardiol 1988;4 Suppl A:5A-10A.
3. Assmann G, et al. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis 1996;124 Suppl:S11-20.
4. Cannon CP, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-1504 [Erratum in N Engl J Med 2006;354:778.]
5. Barter P, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007;357:1301-1310.
6. The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011;365:2255-2267.
7. The Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA 1975;231: 360-381.
8. Rubins HB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999;341:410-418.
Among patients with coronary heart disease and LDL-cholesterol levels less than 70 mg/dL, there is no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up, despite improvements in HDL-cholesterol and triglyceride levels.Subscribe Now for Access
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