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 open-label 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 HDL-C and was well tolerated in Japanese patients with dyslipidemia (ClinicalTrials.gov number NCT01760460).