Jeffrey L Probstfield1, William E Boden2, Todd Anderson3, Kelley Branch1, Moti Kashyap4, Jerome L Fleg5, Patrice Desvigne-Nickens5, Ruth McBride6, Mark McGovern7. 1. Department of Cardiology, University of Washington, School of Medicine, Seattle, WA, USA. 2. VA New England Healthcare System, VA Boston-Jamaica Plain Campus, Boston, MA, USA. 3. University of Calgary and Libin Cardiovascular Institute, Foothills Medical Centre, Calgary, AB, Canada. 4. VA Long Beach Healthcare System, Long Beach, CA, USA. 5. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 6. Axio Research LLC, Seattle, WA, USA. Electronic address: ruthm@axioresearch.com. 7. Miami Beach, FL, USA.
Abstract
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 ofERN treatment did not lower CV event rates. An additional year of follow-up off assigned treatment did not alter these findings.
RCT Entities:
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.