Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia: A meta-analysis of 35 randomized controlled trials

Background--we sought to examine the efficacy and safety of 2 pcsk9 (proprotein convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab. methods and results--we performed a systematic review and meta-analysis of randomized controlled trials comparing treatment with and without pcsk9 inhibitors; 35 randomized controlled trials comprising 45 539 patients (mean follow-up: 85.5 weeks) were included. mean age was 61.0±2.8 years,and mean baseline low-density lipoprotein cholesterol was 106±22 mg/dl. compared with no pcsk9 inhibitor therapy,treatment with a pcsk9 inhibitor was associated with a lower rate of myocardial infarction (2.3% versus 3.6%; odds ratio [or]: 0.72 [95% confidence interval (ci),0.64-0.81]; p < 0.001),stroke (1.0% versus 1.4%; or: 0.80 [95% ci,0.67-0.96]; p=0.02),and coronary revascularization (4.2% versus 5.8%; or: 0.78 [95% ci,0.71-0.86]; p < 0.001). overall,no significant change was observed in all-cause mortality (or: 0.71 [95% ci,0.47- 1.09]; p=0.12) or cardiovascular mortality (or: 1.01 [95% ci,0.85-1.19]; p=0.95). a significant association was observed between higher baseline low-density lipoprotein cholesterol and benefit in all-cause mortality (p=0.038). no significant change was observed in neurocognitive adverse events (or: 1.12 [95% ci,0.88-1.42]; p=0.37),myalgia (or: 0.95 [95% ci,0.75-1.20]; p=0.65),new onset or worsening of preexisting diabetes mellitus (or: 1.05 [95% ci,0.95-1.17]; p=0.32),and increase in levels of creatine kinase (or: 0.84 [95% ci,0.70-1.01]; p=0.06) or alanine or aspartate aminotransferase (or: 0.96 [95% ci,0.82- 1.12]; p=0.61). conclusions--treatment with a pcsk9 inhibitor is well tolerated and improves cardiovascular outcomes. although no overall benefit was noted in all-cause or cardiovascular mortality,such benefit may be achievable in patients with higher baseline lowdensity lipoprotein cholesterol. © 2017 the authors.