Abstract 15068: Comparison of Extended-Release Niacin versus Placebo in Statin-Treated Patients With Low Baseline Levels of HDL-C and Well-Controlled on-Treatment LDL-C: Extended One-Year Follow-Up Outcomes From AIM-HIGH
Background: Epidemiological studies have shown that low levels of HDL-C and high triglycerides (TG) are independent predictors of increased rates of cardiovascular (CV) events, and may account for residual CV risk despite intensive LDL-C lowering therapy. Various drugs (e.g., fibrates, niacin, CETP inhibitors) have been shown to increase HDL-C levels, but no large trials in the “statin era” have proven a definitive benefit of HDL-C raising in reducing CV events.
Methods: The AIM-HIGH trial prospectively randomized 3,414 patients with established atherosclerotic CV disease and low levels of baseline HDL-C (men: <40 mg/dL; women: <50 mg/dL) and TG 150-400 mg/dL to high-dose extended release niacin (ERN) 1,500-2,000 mg/day vs. placebo. All patients received simvastatin ± ezetimibe dose adjusted to achieve and maintain an on-treatment LDL-C target level of 40[[Unable to Display Character: –]]80 mg/dL. The trial was stopped prematurely by the DSMB after a mean 3-year follow-up because of a lack of benefit of ERN on the primary composite endpoint (coronary death, non-fatal MI, ischemic stroke, hospitalization for acute coronary syndrome , or symptom-driven coronary or cerebral revascularization). Ischemic stroke was non-significantly increased with ERN. Patients were followed for clinical events for an additional year, off study-guided treatment.
Results: Of 3,236 patients alive at the end of blinded study treatment 2,613 (81%; ERN=1,312, placebo=1,301) were followed for a mean 1.1 additional years. Almost all (95%) remained on a statin; only 4% continued on niacin. Primary endpoints through a mean 4.1 years of follow-up occurred in 343 participants originally assigned to ERN and 305 originally assigned to placebo (HR 1.11, 95%CI 0.96, 1.30); the overall CV event rate was 5%/yr. The incidence of ischemic stroke was slightly higher in those originally randomized to ERN (2.2%) compared to placebo (1.4%, p=0.07).
Conclusions: Despite an appreciable annualized event rate, in patients with established CV disease and atherogenic dyslipidemia, long-term treatment with ERN did not lower the rate of CV events; this finding persisted more than a year after discontinuation of blinded study treatment. The incidence of ischemic stroke remained low and non-significantly increased with ERN.
- © 2013 by American Heart Association, Inc.