Clinical Geriatrics

American Heart Association Scientific Sessions 2009
November 14-18, 2009
Orlando, FL

Extended-Release Niacin Superior to Ezetimibe in Inducing Regression of Atherosclerosis in At-Risk Patients

Orlando, FL—Extended-release niacin was superior to ezetimibe when added to a statin for inducing regression of atherosclerosis, according to results of the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6: HDL and LDL Treatment Strategies in Atherosclerosis (ARBITER6-HALTS) study. The study was presented at the 2009 Scientific Sessions of the AHA.

“This study establishes that combination therapy with niacin/statin is superior to statin/ezetimibe. In clinical practice, it is prudent to avoid ezetimibe at present because its net effect on clinical outcomes is unknown and its relative effectiveness is now shown to be inferior,” said Allen J. Taylor, MD, Cardiology Service at Walter Reed Army Medical Center, Washington, DC.

In 2008, approximately 9 million adults in the United States received ezetimibe, and only 2.5 million patients received niacin, said Dr. Taylor. The combined sales of ezetimibe and the combination ezetimibe and simvastatin drug were $4.6 billion last year, and sales of niacin were $786 million in the same period. Regression of atherosclerosis was determined by measuring carotid intima-media thickness (CIMT), which is a surrogate marker for atherosclerosis, not a clinical outcome. The study compared two different lipid-modifying strategies in patients at high risk for vascular disease—adding niacin to a statin to increase high-density lipoprotein (HDL)-cholesterol levels versus adding ezetimibe to a statin to further reduce low-density lipoprotein (LDL)-cholesterol levels. Patients (n = 363) with known vascular disease or coronary disease risk equivalents (eg, diabetes mellitus), LDL levels < 100 mg/dL, and moderately low HDL-cholesterol levels (< 50 mg/dL) were randomized to ezetimibe 10 mg/day or to extended-release niacin 2000 mg/day. All patients had been on statin therapy for at least 3 months before randomization. Mean age was 65 years, 80% were male, and median duration of statin use was 6 years. At entry to the study, mean LDL-cholesterol levels were 82 mg/dL, and mean HDL-cholesterol levels were 42.4 mg/dL.

“This is not a ‘low-HDL’ population. The entry HDL level population is representative of 25%-50% of the U.S. female and male populations and mirrors baseline mean HDL cholesterol from published statin secondary prevention trials,” said Dr. Taylor.

After 14 months of treatment, mean HDL-cholesterol levels increased by 18.4% from baseline to 50 mg/dL in the niacin arm (P < 0.001 vs baseline). In the ezetimibe arm, LDL-cholesterol level decreased from 81 mg/dL at baseline to 66 mg/dL (19.2%, P < 0.001 vs baseline). Niacin also significantly reduced LDL-cholesterol and triglycerides from baseline, and ezetimibe also reduced HDL-cholesterol and triglycerides from baseline. The primary end point was change in mean CIMT from baseline to 14 months. The study was terminated early for efficacy based upon a pre-specified interim analysis after 208 subjects completed the trial. Niacin had significantly greater efficacy than ezetimibe for the change in mean CIMT from baseline (P = 0.003). Mean and maximal CIMT significantly regressed in the niacin arm at 14 months (P = 0.001 and P < 0.001, respectively), whereas no significant changes in these measurements were seen in the ezetimibe arm. More major cardiovascular events occurred in those who received ezetimibe: 5.5% versus 1.2%, respectively (P = 0.04), although the study was not powered to assess clinical outcomes.

Dr. Taylor noted that there was a paradoxical increase in CIMT in patients treated with ezetimibe, despite greater reductions in LDL-cholesterol in that arm. “This raises concerns about ezetimibe’s mechanism of action,” he said.