Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6–HDL and LDL Treatment Strategies - ARBITER 6-HALTS
The goal of this trial was to compare treatment with niacin compared with ezetimibe among patients with coronary heart disease (CHD).
Niacin would be more effective in reducing carotid intima-media thickness.
Patients Enrolled: 208
Mean Follow Up: 14 months
Mean Patient Age: 64 years
- 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
- Between group difference in mean common carotid intima-media thickness at 14 months
- 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
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).
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%.
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.
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.
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.
Keywords: Cholesterol, Carotid Intima-Media Thickness, Hyperlipidemias, Azetidines, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Coronary Disease, Niacin, Hypercholesterolemia, Diabetes Mellitus
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