Elsevier

American Heart Journal

Volume 161, Issue 3, March 2011, Pages 471-477.e2
American Heart Journal

Trial Design
The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol: Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH)

https://doi.org/10.1016/j.ahj.2010.11.017Get rights and content

Background

The aim of this study was to test the hypothesis that patients with atherosclerotic cardiovascular (CV) disease optimally treated on a statin but with residual atherogenic dyslipidemia (low high-density lipoprotein cholesterol [HDL-C] and high triglycerides) will benefit from addition of niacin with fewer CV events compared with placebo. Statin monotherapy trials have found 25%-35% CV risk reduction relative to placebo, leaving significant residual risk. Patients with atherogenic dyslipidemia have substantially increased CV risk.

Methods

Participants were men and women with established CV disease and atherogenic dyslipidemia. Lipid entry criteria varied by gender and statin dose at screening. All participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain low-density lipoprotein cholesterol (LDL-C) 40-80 mg/dL (1.03-2.07 mmol/L). Participants were randomized to extended-release niacin or matching placebo. The primary end point was time to occurrence of the first of the following: coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, or symptom-driven coronary or cerebral revascularization. This event-driven trial will have 85% power to show a 25% reduction in primary event frequency after 850 patients have experienced a primary outcome event.

Results

AIM-HIGH completed enrollment in April 2010. Follow-up is expected to continue through 2012.

Summary

AIM-HIGH was designed to determine whether treating residual dyslipidemia with niacin further reduces cardiovascular events in patients with CV disease on a statin at target levels of low-density lipoprotein cholesterol.

Section snippets

Background

Although atherosclerotic cardiovascular (CV) disease mortality has declined significantly over the past 4 decades, it remains the leading cause of death and disability among men and women in the Western world.1 Currently, over 13.2 million Americans have diagnosed coronary heart disease (CHD), and despite profound advances in both pharmacologic and interventional management over the past 15 years, both morbidity and mortality remain appreciable. Elevated low-density lipoprotein cholesterol

Participating clinical sites

Participating sites, identified based on successful recruitment in prior trials, were selected from outpatient internal medicine, cardiology, and diabetes clinics and catheterization and vascular laboratories. Study participants were recruited from 69 sites from the United States and 23 from Canada. Institutions included 33 private, 27 university, and 18 community hospitals; 12 Veterans Administration facilities; and 1 managed care clinic. Predominant recruitment strategies included

Results

AIM-HIGH completed enrollment in April 2010 (Fig. 1). Participants were recruited from the United States, 1,871 (55%) from non–Veterans Administration facilities and 475 (14%) from Veterans Administration facilities, and from Canada, 1,068 (31%). Of the 8,162 participants who signed informed consent, 2,825 were excluded because they did not meet the lipid criteria. The most common reason for exclusion of patients meeting lipid and CV disease entry requirements was unwillingness to discontinue

Discussion

Beginning with the Scandinavian Simvastatin Survival Study in 1994,14 clinical trials with statins have shown major coronary events to decrease in rough proportion to the on-treatment percent reduction in LDL-C and overall by about 30% of the placebo-treated rates.2 Thus, although statins, which principally lower LDL-C, reflect an important therapeutic advance, additional treatment measures are needed to further diminish the health impact of atherosclerotic vascular disease. AIM-HIGH is the

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  • Cited by (0)

    Supported in part by National Institutes of Health, National Heart, Lung, and Blood Institute component grants U01 HL081616 and U01 HL081649, with additional unrestricted grant support and drug supply from Abbott Laboratories, Abbott Park, IL, and by drug supply from Merck, Inc., West Point, PA.

    ClinicalTrials.gov identifier: NCT00120289.

    b

    [email protected]

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