The AIM-HIGH investigators aimed for the lofty target of proving the beneficial effects of niacin therapy. They did not succeed.
The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) investigators randomized 3414 patients with CV disease, low HDL and elevated triglycerides to extended-release niacin or placebo in addition to simvastatin. During the trial niacin increased HDL by 25% and decreased triglycerides by28.6%. In the statin group HDL increased by 9.8% and triglycerides decreased by 28.6%. Results of the trial were presented at the AHA and published simultaneously in the New England Journal of Medicine.
Followup of the trial was stopped early due to futility. The primary endpoint– the first event of the composite of CHD death, nonfatal MI, ischemic stroke, hospitalization for ACS, or symptom-driven coronary or cerebral revascularization– occurred in 16.4% of patients in the niacin group versus 16.2% in the placebo group (HR 1.02, CI 0.87-1.21, p=0.79).
More patients in the niacin group than in the statin group had an ischemic stroke as their primary endpoint event (1.6% versus 0.9%). Although the trend persisted when all ischemic strokes were considered, the investigators noted that the overall ischemic stroke rate was low and the imbalance could reflect a play of chance. They also observed that similar increases have not been found in previous niacin studies.
Speculating about the lack of niacin’s effect in the trial, the investigators noted that the beneficial effects of niacin and gemfibrozil (which also raises HDL) were observed in study populations with much higher LDL levels. Aggressive statin therapy, in addition to other contemporary therapies, “may make it difficult to show incremental clinical benefit” from niacin or other new therapies, the authors wrote. They noted that the true effect of niacin will be definitively assessed in the much larger HPS2-THRIVE study, and that additional studies are underway evaluating other HDL-related therapies.
In an accompanying editorial, Robert Giugliano wonders whether niacin, at 56 years of age, is ready for an early retirement. He writes that the modest difference between the groups of 4-5 mg/dl for HDL would be unlikely to show a large difference in outcomes given the background therapies.
“Given the lack of efficacy shown in this trial, the frequent occurrence of flushing with niacin therapy that some patients find intolerable, and the unresolved question of an increased risk of ischemic stroke, one can hardly justify the continued expenditure of nearly $800 million per year in the United States for branded extended-release niacin.”
Until the final answer about niacin arrives with the HPS2-THRIVE trial, Giugliano endorses a suggestion, proposed in an accompanying perspective by Patricia Maningat and Jan Breslow, that niacin be reserved for statin-intolerant patients.