According to researchers for the HPS2-THRIVE trial, adding a combination of extended-release niacin and laropiprant to effective statin-based low-density lipoprotein (LDL)–lowering therapy was not associated with a reduction in major adverse vascular events. In fact, it was associated with additional serious adverse effects.

A population of 25,673 adult patients with vascular disease were assigned to either 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily, with a primary endpoint consisting of a first vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial revascularization). Follow-up was 3.9 years.

Participants experienced an increase in high-density lipoprotein (HDL; on average 6 mg/dl) and a decrease in LDL (10 mg/dl). Niacin-laropiprant was also linked with reductions in blood pressure, lipoprotein(a) levels, and increased glycated hemoglobin levels. However, no significant changes in major vascular events were reported in the niacin-laropiprant group compared to the placebo arm (13.2% vs. 13.7%; p = 0.29). Additionally, patients assigned niacin did not show a significant increase in the incidence of death from any cause versus placebo (6.2% vs. 5.7%; p = 0.08).

Additionally, niacin was associated with increased diagnosis of diabetes (5.7% vs. 4.3%; p < 0.001) and increased disturbances in diabetes control (11.1% vs. 7.5%; p = 0.001). Other reported negative effects in the niacin-laropiprant group included gastrointestinal, musculoskeletal, and skin-related serious adverse events.

Although the results were distressing, the authors noted that niacin may have a role in certain high-risk patients, but added that clinicians need to truly consider the risk-benefit balance before using the agent.

"In light of the consistency of the results with those from previous trials of niacin alone, we believe that the findings from HPS2-THRIVE are likely to be generalizable to all high-dose niacin formulations," they wrote.

In an accompanying editorial, Donald M. Lloyd-Jones, MD, implored practitioners to carefully assess the routine use of niacin due to the "unacceptable toxicity profile for the majority of patients," and to reassess the niacin/HDL cholesterol causation hypothesis: "Although higher HDL cholesterol levels are associated with better outcomes, it is time to face the fact that increasing the HDL cholesterol level in isolation seems unlikely to offer the same benefit."

HPS2-THRIVE Collaborative Group. N Engl J Med. 2014;371:203-12.
Lloyd-Jones DM. N Engl J Med. 2014;371:271-3.

Keywords: Glycated Hemoglobin A, Myocardial Infarction, Stroke, Follow-Up Studies, Lipoprotein(a), Indoles, Hypolipidemic Agents, Lipoproteins, Blood Pressure, Cholesterol, HDL, Niacin, Diabetes Mellitus

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