Efficacy and safety of PCSK9 inhibition in cardiovascular disease: A meta-analysis of 45 randomized controlled trials

BACKGROUND: Safety concerns about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors make physicians reluctant to prescribe agents for patients. The present aim was to assess the efficacy and safety of alirocumab, evolocumab and bococizumab in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: Medline, the Cochrane Library and Clinicaltrials.gov were searched for 45 randomized controlled trials, involving 97,297 patients. RESULTS: Compared with the control group, PCSK9 inhibitors could significantly reduce low-density lipoprotein cholesterol, total cholesterol, triglycerides and increase high-density lipoprotein cholesterol. Alirocumab was associated with lower incidence of unstable angina (p < 0.05) and myocardial infarction (p < 0.05), compared with the control group. Alirocumab (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.60–0.97, p < 0.05), evolocumab (OR 0.79, 95% CI 0.66–0.95, p < 0.05) and bococizumab (OR 0.60, 95% CI 0.42–0.84, p < 0.05) were associated with lower incidence of stroke, compared with control group. The incidence of injection-site reactions was significantly higher in alirocumab (OR 1.68, 95% CI 1.45–1.93, p < 0.05), evolocumab (OR 1.64, 95% CI 1.41–1.91, p < 0.05) and bococizumab (OR 8.03, 95% CI 6.85–9.41, p < 0.05) group than in the control group. CONCLUSIONS: Alirocumab and evolocumab could ameliorate lipid profile and reduce the risk of cardiac disorders and stroke with satisfactory safety and tolerability. However, injection-site reactions should be paid attention to.