Meta-analysis of Randomized Controlled Trials Assessing the Impact of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies on Mortality and Cardiovascular Outcomes

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by monoclonal antibodies has been shown to reduce low density lipoprotein (LDL-C) but its effects on cardiovascular (CV) outcomes have not been fully described. The aim of this study is to assess the impact of PCSK9 inhibition on mortality and CV outcomes by pooling data from all available randomized clinical trials (RCT) of PCSK9 inhibitors. We conducted a comprehensive search of electronic databases, up to December 1, 2018, for all RCTs comparing PCSK9 inhibition to placebo or ezetimibe in patients with hypercholesterolemia or coronary artery disease receiving maximally tolerated statin for primary or secondary prevention of mortality and cardiovascular outcomes. We used random-effects meta-analyses to summarize the studies. We retained 23 RCTs having included 88,041 patients in primary and secondary prevention. The follow-up ranged from 6 to 36 months. PCSK9 inhibition was not significantly associated with reductions in total mortality (odds ratio [OR] 0.91, 95% confidence interval [CI] 078 to 1.06; p = 0.22) and CV mortality (OR 0.95, 95% CI 0.84 to 1.07; p = 0.37). In contrast, PCSK9 inhibition was associated with reductions in myocardial infarction (OR 0.80, 95% CI 0.71 to 0.91; p <0.0001), stroke (OR 0.75, 95% CI 0.65 to 0.85; p <0.0001), and coronary revascularization (OR 0.82, 95% CI 0.77 to 0.88; p <0.0001). In conclusion, PCSK9 inhibition was associated with reductions in myocardial infarction, stroke, and coronary revascularization. Future analyses may identify high-risk patients who may benefit more from these agents and longer follow-up of current or new trials may show a mortality benefit.