The efficacy advantage of evolocumab (AMG 145) dosed at 140mg every 2weeks versus 420mg every 4weeks 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 140mg administered every 2weeks (Q2W) and 420mg administered every 4weeks (Q4W) are widely used, and both dosing schedules were effective in clinical trials. However, some researchers have speculated that 140mg 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 140mg 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 ≤1.8mmol/L with an relative risk (RR) of 1.09 (95% CI, 1.00 to 1.18) compared with 420mg Q4W in patients who were concomitantly treated with statins. These findings were not significantly different between the 140mg Q2W and 420mg Q4W groups when evolocumab was administered as monotherapy. There was 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 420mg Q4W dosage at lowering lipid concentrations, especially in patients who concomitantly received stable statin therapy.