Little benefit, many harms from niacin, study finds

Taking niacin didn't significantly reduce vascular events and did cause a variety of serious side effects for high-risk patients, a new study found.

More than 25,000 patients with vascular disease were included in the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE). They were randomized to either placebo or 2 g of extended-release niacin and 40 mg of laropiprant, a highly selective prostaoid DP(1) receptor antagonist that decreases flushing but has no affect on lipids, daily. The median follow-up was 3.9 years, and the primary outcome was first major vascular event. Results were published in the July 17 New England Journal of Medicine (NEJM).

At follow-up, patients in the niacin group did have lower LDL cholesterol (average difference, 10 mg/dL) and higher HDL cholesterol (average difference, 6 mg/dL). However, the difference in major vascular events was not significant (13.2% on niacin vs. 13.7% on placebo; rate ratio, 0.96; 95% CI, 0.90 to 1.03). The niacin group had significantly higher rates of a number of serious side effects, including disturbances in diabetes control, new diabetes diagnoses, and problems with the gastrointestinal, musculoskeletal, and skin systems. Infections and bleeding rates were also significantly higher in the niacin group.

The latter 2 adverse effects were unexpected, researchers noted, while the others were in line with previous research. In response to these new findings about adverse effects, the authors of a previous trial of niacin (AIM-HIGH) published a letter in the same issue of NEJM about side effects found in their study. They concluded that the data have certain similarities, especially regarding infections, but that the excess in bleeding was not definitively confirmed, and the difference in drug formulations between the trials should be remembered.

Given the side effects and small benefit for patients in the current study, niacin's only possible usefulness may be in particular patient groups, the HPS2-THRIVE authors concluded. An accompanying editorial went further, saying that “niacin must be considered to have an unacceptable toxicity profile for the majority of patients, and it should not be used routinely,” although it could possibly benefit very high-risk patients who have contraindications to statins, need a fourth-line agent, or have severe hypertriglyceridemia. The ineffectiveness of niacin, along with the results of other studies using agents that raise HDL cholesterol, also undermines the hypothesis that increasing HDL cholesterol in isolation is of benefit in reducing cardiovascular events.