Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6–HDL and LDL Treatment Strategies - ARBITER 6-HALTS

Description:

The goal of this trial was to compare treatment with niacin compared with ezetimibe among patients with coronary heart disease (CHD).

Hypothesis:

Niacin would be more effective in reducing carotid intima-media thickness.

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 208
Mean Follow Up: 14 months
Mean Patient Age: 64 years
Female: 22

Patient Populations:

  • Patients with CHD or CHD risk equivalent (diabetes, 10-year Framingham risk score >20%, or a calcium score >200 for women or >400 for men)
  • On statin monotherapy with LDL cholesterol <100 mg/dl and HDL cholesterol <55 mg/dl for women or <50 mg/dl for men

Primary Endpoints:

  • Between group difference in mean common carotid intima-media thickness at 14 months

Secondary Endpoints:

  • Change in lipids
  • Major adverse cardiovascular events (death, myocardial infarction, revascularization, or admission to the hospital for acute coronary syndrome)
  • Discontinuation of study drug due to adverse event
  • Health-related quality of life

Drug/Procedures Used:

Patients with CHD or CHD risk equivalent were randomized to extended-release niacin 2000 mg daily (n = 97) versus ezetimibe 10 mg daily (n = 111).

Concomitant Medications:

At baseline in the niacin group, the use of aspirin was 97%, beta-blocker was 71%, clopidogrel was 32%, angiotensin-converting enzyme inhibitor was 63%, simvastatin was 54%, and atorvastatin was 40%.

Principal Findings:

Overall, 208 patients were randomized. There was no difference in baseline characteristics between the treatment arms. In the niacin group, the mean age was 64 years, 22% were women, 32% had diabetes, and duration of statin use was 5.2 years.

Total cholesterol was 146 versus 147 mg/dl, low-density lipoprotein (LDL) cholesterol was 81 versus 84 mg/dl, and high-density lipoprotein (HDL) cholesterol was 43 versus 43 mg/dl, respectively for niacin versus ezetimibe.

The primary outcome, change in mean carotid intima-media thickness, was -0.0142 mm in the niacin group versus -0.0007 mm in the ezetimibe group (p = 0.003).

The change in LDL cholesterol was -10.0 mg/dl versus -17.6 mg/dl (p = 0.01), whereas the change in HDL cholesterol was 7.5 mg/dl versus -2.8 mg/dl (p < 0.001), respectively.

Major adverse cardiac events were 1% for niacin versus 5% for ezetimibe (p = 0.04). Among patients who withdrew from the study, the cause was due to adverse drug effect in 62% of the niacin group versus 33% of the ezetimibe group (p = 0.12); adherence was 88% versus 95% (p < 0.001), respectively.

Interpretation:

Among CHD patients on statin therapy, with LDL cholesterol <100 mg/dl and HDL cholesterol <50 mg/dl for men or <55 mg/dl for women, the use of extended-release niacin was beneficial. This agent was superior to ezetimibe in reducing mean carotid intima-media thickness, and raising HDL cholesterol. Adverse drug effects were numerically higher and adherence was lower in the niacin group.

While these results are promising by showing a positive effect on a surrogate outcome, the clinical effects and safety profile of extended-release niacin will need to be more carefully studied in properly powered clinical trials.

References:

Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009;Nov 15:[Epub ahead of print].

Presented by Dr. Allen J. Taylor at the American Heart Association Scientific Sessions, Orlando, FL, November 16, 2009.

Clinical Topics: Dyslipidemia, Noninvasive Imaging, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Echocardiography/Ultrasound

Keywords: Cholesterol, Carotid Intima-Media Thickness, Hyperlipidemias, Azetidines, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Coronary Disease, Niacin, Hypercholesterolemia, Diabetes Mellitus


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