The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6–HDL and LDL Treatment Strategies in Atherosclerosis): Final Results and the Impact of Medication Adherence, Dose, and Treatment Duration

Abstract

This report describes the final results of the ARBITER 6-HALTS (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis) trial. The ARBITER 6-HALTS trial was terminated early on the basis of a pre-specified interim analysis showing superiority of niacin over ezetimibe on change in carotid intima-media thickness (CIMT). After termination, an additional 107 subjects completed a close-out assessment. Patients with coronary heart disease (CHD) or CHD equivalent with low-density lipoprotein cholesterol <100 mg/dl and high-density lipoprotein cholesterol <50 mg/dl for men or 55 mg/dl for women while receiving stable statin treatment were randomly assigned to ezetimibe (10 mg/day) or extended-release niacin (target dose, 2,000 mg/day). The primary end point was change in mean CIMT, analyzed according to a last observation carried forward method. The relationships of study medication adherence, dosage, and cumulative exposure (product of adherence, dose, and time) with change in CIMT were explored. Results in 315 patients included 208 with 14-month follow-up and 107 after mean treatment of 7 +/- 3 months. Niacin (n = 154) resulted in significant reduction (regression) in mean CIMT (-0.0102 +/- 0.0026 mm; p < 0.001) and maximal CIMT (-0.0124 +/- 0.0036 mm; p = 0.001), whereas ezetimibe (n = 161) did not reduce mean CIMT (-0.0016 +/- 0.0024 mm; p = 0.88) or maximal CIMT (-0.0005 +/- 0.0029 mm; p = 0.88) compared with baseline. There was a significant difference between ezetimibe and niacin treatment groups on mean changes in CIMT, favoring niacin, for both mean CIMT (p = 0.016) and maximal CIMT (p = 0.01). Increased cumulative drug exposure was related to regression of CIMT with niacin, and progression of CIMT with ezetimibe. Niacin induces regression of CIMT and is superior to ezetimibe for patients taking statins. (Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis; NCT00397657).