Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial

The Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial of patients at high risk of vascular disease found that adding extended-release niacin-laropiprant to intensive statin-based LDL-lowering therapy had no benefit on cardiovascular outcomes. However, the trial also identified previously unrecognized serious adverse effects (including new-onset diabetes, bleeding, and infection). Our objective was to explore the safety profile of niacin-laropiprant and examine whether any patients were at lower (or higher) risk of its adverse effects. HPS2-THRIVE was a randomized, double-blind trial of niacin-laropiprant (2000/40 mg/d) versus placebo among 25,673 patients at high risk of vascular disease. Information on all serious adverse events was collected during a median of 3.9 years of study treatment. Effects of niacin-laropiprant on new-onset diabetes, disturbances of diabetes control, bleeding, infection, and gastrointestinal upset were estimated by (1) time after randomization, (2) severity, (3) baseline characteristics, (4) baseline risk of the adverse event of interest, and (5) risk of major vascular event. The hazard ratio (HR) for new-onset diabetes with niacin/laropiprant was 1.32 (95% CI, 1.16–1.51; P