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Statin plus niacin or ezetimibe?
Raising HDL-cholesterol (HDL-C) with niacin plus a statin is superior to lowering LDL-cholesterol (LDL-C) with ezetimibe plus statin in reversing atherosclerosis according to the widely reported ARBITER trial published on-line in the New England Journal of Medicine in November and simultaneously reported at the American Heart Association meeting in Orlando, FL. The trial enrolled more than 200 patients with coronary heart disease or a coronary heart disease equivalent who were receiving long-term statin therapy with an LDL-C < 100 mg/dL along with an HDL-C < 50 mg/dL for men or 55 mg/dL for women. The patients were randomly assigned to receive extended-release niacin (target is 2000 mg/day) or ezetimibe (10 mg/day). The primary endpoint was the difference in change from baseline in mean and maximal carotid intima-media thickness after 14 months. The trial was terminated early in July of 2009. Both drugs were effective in their roles — the mean HDL-C in the niacin group increased by 18.4% over the 14-month study period (P < 0.001) and the mean LDL-C level in the ezetimibe group decreased by 19.2% (P < 0.001). Niacin significantly reduced LDL-C and triglycerides as well, while ezetimibe lead to a reduction in HDL-C and triglycerides. Niacin was superior to ezetimibe in reducing the primary endpoint, leading to a reduction of both mean (P = 0.001) and maximal carotid intima-media thickness (P ≤ 0.001 for all comparisons). Paradoxically, greater reductions in LDL-C seen with ezetimibe were significantly associated with increases in the carotid intima-media thickness. The incidence of major cardiovascular events was also lower in the niacin group than in the ezetimibe group (1% vs 5%; P = 0.04 by the chi square test) (published on-line at: www.nejm.org; Nov. 15, 2009).
The study has received enormous attention not only because of the primary endpoint, but also because of the significant reduction in major adverse cardiac events in the niacin group, even though the numbers were quite small. At least one editorialist laments the early termination of the study and feels that it is impossible to make recommendations regarding the "adjuvant agent of choice" based on the small numbers (The HALTS Trial — Halting Atherosclerosis or Halted Too Early; published on-line at: www.nejm.org; Nov. 15, 2009). Still, this study provides enough evidence to consider adding niacin to a statin in patients who are at risk of or have low HDL-C. It also deals another blow to ezetimibe (Zetia®) and its partner drug ezetimibe/simvastatin (Vytorin®).