Niacin added to statin therapy doesn't reduce cardiovascular events, study finds

Adding niacin to statin therapy didn't reduce cardiovascular events in high-risk patients despite improvements in cholesterol levels, a new study found.
The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial tested whether extended-release niacin added to intensive statin therapy would further reduce the risk of cardiovascular events in patients with established atherosclerotic cardiovascular disease and atherogenic dyslipidemia (low levels of HDL cholesterol, elevated triglyceride levels, and small, dense particles of LDL cholesterol).
Patients were recruited at 92 clinical centers in North America. Eligible patients were 45 years of age or older and had established cardiovascular disease. All eligible patients had low baseline levels of HDL cholesterol (<40 mg/dL [<1.03 mmol/L] for men or <50 mg/dL [<1.29 mmol/L] for women), elevated triglyceride levels (150 to 400 mg/dL [1.69 to 4.52 mmol/L]), and LDL cholesterol levels lower than 180 mg/dL (<4.65 mmol/L) if they were not taking a statin at entry.
Results appeared online Nov. 16 in the New England Journal of Medicine.
Patients in the niacin group received niacin at a dose of 1,500 to 2,000 mg per day plus simvastatin. Patients in the placebo group received simvastatin plus a matching placebo that contained a small dose (50 mg) of immediate-release niacin in each 500-mg or 1,000-mg tablet to blind treatment for patients and study personnel. In both groups, the dose of simvastatin was adjusted to achieve and maintain LDL cholesterol level in the range of 40 to 80 mg/dL (1.03 to 2.07 mmol/L). Subjects in both groups could receive ezetimibe, at a dose of 10 mg per day, to achieve the target LDL cholesterol level.
A total of 3,414 patients were randomly assigned to receive niacin (n=1,718) or placebo (n=1,696). At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg/dL (0.91 mmol/L) to 42 mg/dL (1.08 mmol/L), lowered the triglyceride level from 164 mg/dL (1.85 mmol/L) to 122 mg/dL (1.38 mmol/L), and lowered the LDL cholesterol level from 74 mg/dL (1.91 mmol/L) to 62 mg/dL (1.60 mmol/L).
The primary end point, a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom-driven coronary or cerebral revascularization, occurred in 282 patients in the niacin group (16.4%) and in 274 patients in the placebo group (16.2%) (hazard ratio, 1.02; 95% CI, 0.87 to 1.21; P=0.79 by the log-rank test). The trial was stopped after three years because of a lack of efficacy.
The authors wrote, "Although previous studies of niacin have shown apparent benefits both in surrogate outcome measures (improvements in carotid intima-media thickness and regression of angiographic coronary-artery stenoses) and in clinical outcomes, we observed no clinical benefit with extended-release niacin in patients with established coronary heart disease and low levels of baseline HDL cholesterol."
An editorial noted, "The disappointing results of AIM-HIGH do not provide support for the use of niacin as an add-on therapy to statins in patients with preexisting stable cardiovascular disease who have well-controlled LDL cholesterol levels. Given the lack of efficacy shown in this trial, the frequent occurrence of flushing with niacin therapy that some patients find intolerable, and the unresolved question of an increased risk of ischemic stroke, one can hardly justify the continued expenditure of nearly $800 million per year in the United States for branded extended-release niacin." A more appropriate use for niacin would be in statin-intolerant patients, the editorial noted.