Lipid-modifying efficacy and tolerability of anacetrapib added to ongoing statin therapy in Japanese patients with dyslipidemia

Background and aims: We aimed to assess the effects of cholesteryl ester transfer protein inhibitor anacetrapib added to statin +/- other lipid-modifying therapies (LMT) in Japanese patients with dyslipidemia who were not at their LDL-C goal. Methods: Patients on a stable dose of statin +/- other LMT with LDL-C >= 100 mg/dL to < 145 mg/dL, >= 120 mg/dL to < 165 mg/dL, >= 140 mg/dL or >= 160 mg/dL for patients with a history of coronary heart disease (CHD), high-, moderate-and low-risk patients respectively, were randomized 2: 1, stratified by background therapy, to double-blind anacetrapib 100 mg (n = 204) or placebo (n = 103) for 24 weeks, followed by a 28-week open-label extension phase (anacetrapib 100 mg) and a 12-week off-drug safety follow-up phase. The primary endpoint was percent change from baseline in LDL-C (beta-quantification method), as well as the safety profile of anacetrapib at Week 24; HDL-C was a key secondary endpoint. Results: Anacetrapib 100 mg further reduced LDL-C (38.0%), non-HDL-C (35.1%), ApoB (28.7%), and Lp(a) (48.3%) and increased HDL-C (148.9%) and ApoAI (50.7%) versus placebo (p < 0.001 for all). There were no meaningful differences between the groups in the proportion of patients with liver enzymes elevations (2.0% vs. 0%), creatine kinase elevations overall (0.5% vs. 0%) or with muscle symptoms (0.5% vs. 0%), blood pressure, electrolytes or adjudicated cardiovascular events (0.5% vs. 0%). In the openelabel period, sustained effects on lipid parameters were observed with anacetrapib and the treatment was generally well tolerated. Conclusions: Long-term treatment with anacetrapib 100 mg substantially reduced LDL-C, increased HDLC and was well tolerated in Japanese patients with dyslipidemia (ClinicalTrials. gov number NCT01760460). (C) 2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. and Tamio Teramoto, Hiroyuki Daida, Katsunori Ikewaki, Hidenori Arai. Published by Elsevier B.V.