Efficacy and safety of proprotein covertase subtilisin/kexin type 9 inhibitors among patients with acute coronary syndrome: a meta-analysis of randomized controlled trials

Abstract

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have formed part of the armamentarium of lipid-lowering therapy, most especially low-density lipoprotein-cholesterol (LDL-C) reduction, which in turn decreases the risk of atherosclerotic cardiovascular diseases and adverse cardiovascular events. However, studies are sparse on the benefit of initiating PCSK9 inhibitors during the early phase of an acute coronary sydrome (ACS). Purpose The objective of this meta-analysis is to investigate the efficacy and safety of the PCSK9 inhibitors evolocumab and alirocumab in the acute setting of an ACS. Methods A systematic search for randomized controlled trials (RCTs) that involve the use of PCSK9 inhibitors in ACS was done using MEDLINE/PubMed and Cochrane Library. Results Three RCTs (n=385 participants) were included in this meta-analysis comparing PCSK9 inhibitors versus placebo in patients hospitalized for ACS. Among patients being managed for ACS, PCSK9 inhibitors demonstrated a greater reduction in LDL-C compared to placebo as early as day 3 (WMD −41.65%, 95% CI [−60.09, −23.21], p<0.00001), and was maintained until week 4 (WMD −45.67%, 95% CI [−64.82, −26.53], p<0.00001). The occurrence of adverse events did not significantly differ between the two groups in terms of hospitalization for recurrent ACS (OR 0.99, 95% CI 0.10–9.98, p=1.0), hospitalization for heart failure (OR 6.18, 95% CI 0.26–146.78, p=0.26), or cerebrovascular events (OR 3.12, 95% CI 0.31–31.30, p=0.33). Conclusion In patients admitted for ACS, the early administration of PCSK9 inhibitors such as evolocumab and alirocumab during the first 24 hours of hospitalization resulted in a rapid and significant reduction of LDL-C without any significant adverse event as compared to placebo. Further validation of the role of PCSK9 inhibitors in the setting of ACS is needed to robustly investigate its contribution in improving hard cardiovascular outcomes. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): St. Luke's Medical Center Global City