Effects of alirocumab on cardiovascular events and all-cause mortality: a systematic review and meta-analysis

Jinghui Bai,Wanting Wang,Zhaoqiang Feng

doi:10.31083/j.rcm2203093

Abstract

Evaluation of the effects of alirocumab on cardiovascular (CV) events, CV mortality and all-cause mortality. Data search was carried out using the Cochrane Library, PubMed, Web of Science and Embase. The search time is up to November 18, 2020. All randomized clinical trials (AEs) comparing alirocumab with placebo were searched. Meta-analysis was performed by Review Manager version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark), and the heterogeneity between studies was tested by Cochrane's Q test and measured with I2 statistics. A total of 13 randomized controlled trials with 24,815 participants were included. Alirocumab usage can considerably lower the incidence of CV events when compared to the control group (risk ratio(RR) 0.89, 95% confidence interval(CI) 0.83-0.95). No significant difference in CV mortality between the two groups was observed (RR 0.87, 95% CI 0.74-1.04). Treatment with alirocumab has been associated with a major decrease in all-cause mortality compared to placebo (RR 0.80, 95% CI 0.66-0.96). The incidence of serious adverse events (AEs) was similar in the two groups (RR 0.94, 95% CI 0.90-0.99). Alirocumab can reduce CV events and all-cause mortality. The AEs were mild and tolerable.

Highlights

Both in Western countries and some Eastern countries, cardiovascular (CV) disease has been the main cause of death in recent years [1, 2]
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease that promotes the degradation of LDL receptors and decreases the ability of the liver to remove LDL cholesterol (LDLC) from circulation [6, 7]
Meta-analysis has evaluated the effect of PCSK-9 inhibitors on incidence of CV disease and all-cause mortality [10, 11], there is no systematic meta-analysis to directly assess the impact of alirocumab on CV events

Summary

Introduction

Both in Western countries and some Eastern countries, cardiovascular (CV) disease has been the main cause of death in recent years [1, 2]. The level of LDL cholesterol (LDLC) in plasma is one of the main risk factors for CV [3]. Alirocumab inhibits hepatic LDLR degradation, increases liver clearance of LDLC, and reduces plasma LDL-C concentration by binding to circulating PCSK9 [8]. Randomized controlled trial (RCT) data from ODYSSEY results indicate that alirocumab has significant clinical benefits in subjects at high CV risk [9]. Alirocumab did not reduce the incidence of CV events compared with ezetimibe in the ODYSSEY COMBO II trial. Meta-analysis has evaluated the effect of PCSK-9 inhibitors on incidence of CV disease and all-cause mortality [10, 11], there is no systematic meta-analysis to directly assess the impact of alirocumab on CV events. 30.0 ± 5.4 hypercholesterolaemia and established CHD Cannon 2015 [12]

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Conclusion