The efficacy advantage of evolocumab (AMG 145) dosed at 140 mg every 2 weeks versus 420 mg every 4 weeks in patients with hypercholesterolemia: Evidence from a meta-analysis

Background: Evolocumab (AMG 145), a PCSK9 inhibitor, has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels. Doses of 140 mg administered every 2 weeks (Q2W) and 420 mg administered every 4 weeks (Q4W) are widely used, and both dosing schedules were effective in clinical trials. However, some researchers have speculated that 140 mg Q2W administration has equal or even greater efficacy. This meta-analysis was performed to assess the differences in efficacy and safety between the two doses. Methods: We searched the PubMed, EMBASE, and Web of Science databases to identify relevant clinical trials published before January 2016. A total of 2403 patients from 8 randomized controlled trials were identified and included in the analysis. Results: Evolocumab administered at 140 mg Q2W resulted in a greater percent change from baseline in LDL-C concentration (-7.27; 95% confidence interval (CI), -10.36 to -4.18) and had greater efficacy in achieving the treatment goal of LDL-C <= 1.8 mmol/L with an relative risk (RR) of 1.09 (95% CI, 1.00 to 1.18) compared with 420 mgQ4Win patients whowere concomitantly treated with statins. These findings were not significantly different between the 140 mg Q2W and 420mg Q4W groups when evolocumab was administered asmonotherapy. Therewas no difference in the rate of occurrence of the main treatment-related adverse events between the two doses. Conclusions: Evolocumab administered at 140mg Q2W was more effective than the 420 mg Q4W do sage at lowering lipid concentrations, especially in patients who concomitantly received stable statin therapy. (C) 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.