Adding niacin and laropiprant to statins in patients with atherosclerotic vascular disease increased the risk of adverse events without providing therapeutic benefits compared to statins and a placebo, according to results from the HPS2-THRIVE trial.

Writing in the July 17 issue of the New England Journal of Medicine, the HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events) team reported results from the randomized, double-blind, multicenter trial. The analysis included 25,673 high-risk patients with known vascular disease who were tolerant of niacin-laropiprant treatment.

High-dose niacin decreases low-density lipoprotein (LDL) levels while boosting high-density lipoprotein (HDL) levels. Laropiprant helps reduce flushing that can occur in some patients who take niacin.

Patients were randomized to receive either 2 g of niacin, 40 mg of laropiprant and a statin or a placebo plus a statin. The primary outcome was the first major vascular event, which included a major coronary event, a stroke or coronary or noncoronary revascularization.

The patients had a median age of 64.9 years and 82.7 percent were men. More patients in the niacin group discontinued medication (25.4 percent vs. 16.6 percent for the control). The niacin group had an average reduction of 10 mg per deciliter in their LDL cholesterol levels and an average increase of 6 mg per deciliter in their HDL cholesterol levels.

Nonetheless, at a median follow-up of 3.9 years the HPS2-THRIVE researchers found no significant reduction in the incidence of major adverse vascular events. The rate for the niacin group was 13.2 percent vs. 13.7 percent for the control group.

The results highlighted a litany of hazards, though. Compared with placebo, niacin had a nonsignificant 9 percent increase in death from any cause and a nonsignificant increase in death from vascular and nonvascular causes.

The niacin group experienced a higher proportion of adverse events, including:

• Gastrointestinal events, 4.8 percent vs. 3.8 percent;
• Musculoskeletal, 3.7 percent vs. 3 percent;
• Infections, 8 percent vs. 6.6 percent; and
• Bleeding events, 2.5 percent vs. 1.9 percent.

The niacin group had more newly diagnosed cases of diabetes (5.7 percent vs. 4.3 percent) and serious complications with glucose control in those with existing diabetes (11.1 percent vs. 7.5 percent).

“Although niacin might still be relevant for particular patient groups (e.g., patients at high risk for vascular events who have high levels of LDL cholesterol), any potential benefits should be considered in the context of the observed hazards,” the researchers cautioned.

The study was funded by Merck.