Niacin: a long history, but a questionable future.

PURPOSE OF REVIEW: To provide an update on recent mechanistic and clinical trial data related to the actions and efficacy of niacin.

RECENT FINDINGS: Recent mechanistic studies have provided novel insights regarding the mechanism of action of niacin. Studies of the purported niacin receptor, GPR109A, indicate that niacin-mediated fatty acid-lowering and flushing are dependent on niacin binding to this receptor, whereas the lipid-altering effects of niacin may be independent of the interaction of niacin with the receptor. Two cardiovascular outcome trials - Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health trial and HPS2-THRIVE - were both negative.

SUMMARY: Niacin has been used to treat dyslipidemia for almost 60 years. Recent studies have provided clues to niacin's broad lipid-altering efficacy, but more work is required to fully understand its mechanisms of action. The failure of niacin to reduce cardiovascular events in two recent placebo-controlled trials of high-risk patients with LDL-cholesterol levels less than 70 mg/dl on statins was surprising based on prior outcome and surrogate studies. We await publication of subgroup analyses to allow full assessment of those trials. In the meantime, we should not forget that niacin is an effective LDL-cholesterol-lowering drug in patients with high LDL levels despite statin treatment.