Clinical Investigation
Prevention and Rehabilitation
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: Baseline characteristics of study participants. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH) trial

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Objectives

The study aims to report the baseline characteristics of the fully randomized AIM-HIGH study population.

Background

Residual risk persists despite aggressive low-density lipoprotein cholesterol (LDL-C) reduction in patients with atherosclerotic cardiovascular (CV) disease, many of whom have atherogenic dyslipidemia (low levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and small dense LDL particles).

Methods

All study participants had established CV disease and atherogenic dyslipidemia. Participants received simvastatin (or simvastatin plus ezetimibe) at a dose sufficient to maintain LDL-C at 40 - 80 mg/dL (1.03-2.07 mmol/L) and were randomized to receive extended-release niacin or matching placebo. The primary end point is time to the first occurrence of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome or symptom-driven coronary or cerebral revascularization with average follow-up of 4.1 years.

Results

Between 2006 and 2010, 8,162 individuals signed consent to be screened, 4,275 began study drug run-in, and 3,414 were randomized to treatment. Mean age at entry was 64 ± 9 years, 85% were men, and 92% were white. As expected, risk factors were prevalent with 34% having diabetes; 71%, hypertension; and 81%, metabolic syndrome. Most participants had coronary artery disease (92%), whereas 11% had peripheral arterial disease; and 12%, cerebrovascular disease. Previous coronary revascularization occurred in 82%, and 54% reported a prior myocardial infarction. Among participants on a statin at entry (94%), mean baseline LDL-C was 71 mg/dL (1.84 mmol/L); mean HDL-C, 34.9 mg/dL (0.90 mmol/L); and median triglycerides, 161 mg/dL (1.82 mmol/L).

Summary

AIM-HIGH enrolled a high-risk group of patients with established atherosclerotic CV disease and atherogenic dyslipidemia. This study should determine whether there is incremental clinical benefit of niacin in reducing cardiovascular events in patients who have attained optimal on-treatment levels of LDL-C with a statin.

Section snippets

Background

Atherogenic dyslipidemia is an important and increasing cause of cardiovascular risk. It is characterized by a high-risk phenotype with associated low levels of high-density lipoprotein cholesterol (HDL-C), high triglycerides, and small dense low-density lipoprotein (LDL) particles often in the setting of insulin resistance and metabolic syndrome.1 Extensive clinical trial evidence has established 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors (statins) as the backbone of preventive

Methods

AIM-HIGH is a double-blind, randomized, controlled clinical trial designed to examine the hypothesis that treatment with extended-release niacin in patients with optimally controlled LDL-C levels (40-80 mg/dL) would decrease the rate of cardiovascular events (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome or symptom-driven coronary or cerebral revascularization) in patients with a documented history of atherosclerotic

Results

Results of screening are described in the companion design manuscript. Briefly, 8,162 participants signed informed consent to be screened, 4,275 were eligible and began open-label run-in on extended-release niacin, and 3,414 were randomized.

Among the 3,569 men and 706 women enrolled into the open-label run-in, 2,910 men (82% of those enrolled) and 504 women (71% of those enrolled) were ultimately randomized to extended-release niacin or placebo. The difference between the proportions of men and

Discussion

AIM-HIGH is the first large randomized trial to evaluate the effect of niacin on cardiovascular events among statin-treated patients with established atherosclerotic cardiovascular disease who are at goal for LDL-C but who have residual abnormalities in HDL-C and triglycerides (ie, so-called atherogenic dyslipidemia). Previous studies with niacin as secondary prevention have several limitations. The Coronary Drug Project,19 the only large placebo-controlled trial of niacin monotherapy, enrolled

References (27)

  • GinsbergH.N. et al.

    Effects of combination lipid therapy in type 2 diabetes mellitus

    N Engl J Med

    (2010)
  • Effects of intensive glucose lowering in type 2 diabetes

    N Engl J Med

    (2008)
  • SorrentinoS.A. et al.

    Endothelial-vasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy

    Circulation

    (2010)
  • 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, Illinois, and by drug supply from Merck, Inc, West Point, Pennsylvania.

    Clinicaltrials.gov Identifier: NCT00120289.

    b

    [email protected]

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