Niacin: Time to Believe Outcomes Over Surrogate Outcomes

Abstract

Long-acting niacin, a blockbuster drug for many years, emerged during an era in which the simple assumption was that favorably modifying patients’ lipid profiles was tantamount to lowering their risks for cardiovascular disease. The implicit assumption in the medical community and among regulators was that improving lipid profiles would improve outcomes even as the mechanism of the drug action was not clear. This approach holds sway today as evidenced by the recent approval of the PCSK9 inhibitor drugs before the completion of the definitive phase 3 outcome trials.1,2 The evidence suggests that the way in which a risk factor is modified matters for whether it produces a benefit.3 Long-acting niacin is a particularly interesting case because it was included in one of the earliest outcome trials, the Coronary Drug Project, initiated in 1966, although the results were equivocal.4 With 5 to 8 years of follow-up, niacin failed to improve mortality, the primary end point. The 5-year rates of death were 21.2% for niacin and 20.9% for placebo. Death rates because of coronary heart disease were also close and not significantly different: 15.9% for niacin and 16.2% for placebo. The niacin group did have a lower risk of nonfatal myocardial infarction, one of the secondary end points. It should also be noted that because …