Adding Niacin to Statin Therapy for Patients with Low HDL-C Levels

Citing statistics that >18 million North Americans have coronary heart disease, researchers note that despite advances in pharmacologic as well as diet and lifestyle interventions, morbidity and mortality from cardiovascular disease remain high. Elevation in low-density lipoprotein cholesterol (LDL-C) levels is a major risk factor for coronary heart disease. Statin therapy has been shown to reduce the risk by 25% to 35%, but residual risk remains after patients achieve target LDL-C levels. A low level of high-density lipoprotein cholesterol (HDL-C) is also an independent predictor of risk for coronary heart disease. It remains unclear whether adding extended-release niacin to simvastatin to raise HDL-C levels is superior to simvastatin alone in reducing the residual risk of coronary heart disease associated with low HDL-C levels. The researchers recently conducted the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial to test whether adding extended-release niacin to intensive statin therapy would reduce the risk of heart disease in patients with established atherosclerotic cardiovascular disease and atherogenic dyslipidemia (defined as low levels of HDL-C, elevated triglyceride levels, and small, dense particles of LDL-C). They reported study results in the New England Journal of Medicine [2011;365(24):2255-2267]. The study’s primary end point was the first event of the composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for >23 hours for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. Secondary composite end points were death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or hospitalization for a high-risk acute coronary syndrome; death from coronary heart disease, nonfatal myocardial infarction, or ischemic stroke; and death from cardiovascular causes. Study participants were randomly assigned to 1 of 2 study groups: 1718 to a group receiving niacin at a dose of 1500 to 2000 mg/day plus simvastatin (niacin group) and 1696 to a group receiving simvastatin plus a matching placebo that contained a small dose (50 mg) of immediate-release niacin in each 5000- or 1000-mg tablet to maintain blinding (placebo group). Mean age was 64 years, 85.2% were men, 92.2% were white, 33.9% had diabetes, 71.4% had hypertension, and 81.0% had the metabolic syndrome. Baseline characteristics were similar in both groups. At entry, 93.6% of study participants (n=3196) were taking a statin. Of those, the baseline median LDL-C level was 71 mg/dL, median HDL-C level was 35 mg/dL, and median triglyceride level was 161 mg/dL. Among patients not taking a statin at baseline (n=218), baseline LDL-C level was 124 mg/dL, HDL-C level was 33 mg/dL, and triglyceride level was 215 mg/dL. At the 2-year follow-up, the HDL-C level in the niacin group had increased by 25.0% to 42 mg/dL, compared with an increase of 9.89% to 38 mg/dL in the placebo group (P<.001). LDL-C levels decreased by 12.0% in the niacin group and by 5.5% in the placebo group. Decreases in triglyceride levels were 28.6% in the niacin group versus 8.1% in the placebo group. The primary end point occurred in 16.4% of patients in the niacin group (n=282) and 16.2% of patients in the placebo group (n=274), resulting in a hazard ratio with niacin of 1.02; P=.80 for the superiority of niacin therapy with the use of a Cox proportional-hazards model and P=.79 by the log-rank test. In the niacin group there was a similar lack of efficacy on the composite secondary end point of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or hospitalization for a high-risk acute coronary syndrome (hazard ratio, 1.08; P=.49) and on the composite secondary end point of death from coronary heart disease, nonfatal myocardial infarction, or ischemic stroke (hazard ratio, 1.13; P=.30). The study was stopped after a mean follow-up period of 3 years due to a lack of efficacy.