Further information: Coronary Risk Factors: An Overview (see p2609) and Management of Cholesterol Disorders (see p2667) from Cardiovascular Medicine, 3rd Edn*

In a presentation of results from a controversial late-breaking clinical trial at the November 2009 American Heart Association Scientific Sessions in Orlando, Florida, Dr. Allen Taylor reported that the ARBITER6-HALTS (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies) trial had been terminated early. The full results are summarized in the first paper [1]. The study, which enrolled 363 patients, involved using either ezetimibe or extended-release niacin. The patients had at a high risk for atherosclerotic vascular disease and were already receiving statin therapy. They also had a serum LDL cholesterol level (<100 mg/dL), as well as a low serum HDL level (mean, 42 mg/dL). The patients in this open-label randomized trial of two adjunctive medications were randomly assigned to receive either extended-release niacin (target dose was 2000 mg/day) or ezetimibe (10 mg/day). A surrogate marker for the progression of atherosclerosis (identified as a change in the common-carotid intima-media thickness) was the primary endpoint.

Because the trial was terminated early on the basis of efficacy, data from only 208 patients were available for analysis. However, on the basis of the small sample size and the with the use of a surrogate marker, both of which created controversy, the authors reported the following conclusions. In the niacin group, the mean HDL cholesterol level increased by 18.4%, and the mean LDL cholesterol and triglyceride level were significantly reduced. In the ezetimibe group, LDL cholesterol was reduced by 19.2%. A paradoxical finding regarding ezetimibe indicated that an association between reduction in the patient’s LDL level was accompanied by an increased carotid intima-media thickness. Based on these results the authors concluded that niacin therapy was superior to ezetimibe.

Two editorials were published with the article. Blumenthal and Michos [2] raised four major concerns regarding the trial and expressed the opinion that premature termination of the trial, a small number of patients, and limited follow-up precluded a statement of decisive conclusions. Kastelein and Bots [3] expressed that although the trial had several limitations, the results were likely to be correct. Both editorials pointed to additional studies currently underway that, when concluded, will produce results likely to aid in the evaluation of the use of niacin and statin therapies.

[1] Taylor AJ, Villines TC, Stanek EJ, et al. Extended release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009;361:2113-22

[2] Blumenthal RS, Michos ED. The HALTS trial—halting atherosclerosis or halting too early? N Engl J Med 2009;361:2178-80

[3] Kastelein JJP, Bots ML. Statin therapy with ezetimibe or niacin in high-risk patients. N Engl J Med 2009;361:2180-83

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