Cardiovascular outcomes during extended follow-up of the AIM-HIGH trial cohort.

Background: Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) and elevated triglycerides are independent predictors of cardiovascular (CV) events, though randomized trials of HDL-C-raising therapies to reduce clinical events have been largely disappointing. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial failed to show that extended release niacin (ERN) reduced CV events in patients with atherogenic dyslipidemia who were on statin-based therapy.

Objective: We sought to determine whether extended follow-up of AIM-HIGH participants changed these null results.

Methods: AIM-HIGH was a placebo-controlled trial of 3414 patients with established CV disease, low baseline HDL-C, and elevated triglycerides levels randomized to ERN 1500-2000 mg/d vs placebo. Participants also received simvastatin with or without ezetimibe to attain on-treatment low-density lipoprotein cholesterol levels of 40-80 mg/dL. The trial was halted after a mean 3-year follow-up because of futility.

Results: Among 3236 participants alive at the end of blinded study, 2613 (81%; ERN = 1,312, placebo = 1301) were followed a mean 1.1 additional years. Ninety-five percent of subjects remained on statin, but only 4% on ERN. At a mean total follow-up of 4.1 years, there were 343 primary CV endpoints in the ERN arm and 305 CV endpoints in placebo participants (HR 1.11, 95% CI 0.96, 1.30). Ischemic stroke was also not significantly different after extended follow-up in the two groups (2.2% vs 1.5%, P = .13).

Conclusions: In patients with CV disease and atherogenic dyslipidemia on statin-based therapy, 3 years of ERN treatment did not lower CV event rates. An additional year of follow-up off assigned treatment did not alter these findings.