SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Drugs Outcomes Research and Policies
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1555508
Indirect Comparison of the Efficacy and Safety of Alirocumab and Evolocumab on Major Cardiovascular Events: A Systematic Review and Network Meta-analysis
Provisionally accepted
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Background: Alirocumab and evolocumab are proprotein convertase subtilisin/kexin type 9 inhibitors that significantly reduce the relative risk of cardiovascular events. However, the relative efficacy and safety of alirocumab and evolocumab in different patient groups still warrant further indirect comparison. This systematic review and network meta-analysis indirectly compared the efficacy and safety of alirocumab and evolocumab on major cardiovascular events. Methods: PUBMED, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were comprehensively searched to extract randomized controlled trials (RCTs) regarding alirocumab and evolocumab published from inception to August 17, 2024. The meta-analysis was performed using Software Review Manager 5.4 and R 4.1.0 software. Results: This network meta-analysis included 26 RCTs with 64921 patients. Among these, 13 RCTs included patients receiving alirocumab or placebo (n=13365) and 13 RCTs included patients receiving evolocumab or placebo (n=22048). Compared with the placebo, treatment with alirocumab and evolocumab significantly reduced the relative risk of major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction, stroke, and coronary revascularization. Furthermore, alirocumab and evolocumab groups did not show significant differences in MACCE [relative risk (RR): 0.99, 95% confidence interval (CI): 0.88-1.11], cardiovascular death (RR: 0.83, 95% CI: 0.65-1.06), myocardial infarction (RR: 0.87, 95% CI: 0.74-1.03), stroke (RR: 0.96, 95% CI: 0.71-1.29), coronary revascularization (RR: 0.88, 95% CI: 0.77-1.01), and any adverse event (RR: 0.91, 95% CI: 0.76-1.09). Moreover, the all-cause mortality rates were lower for patients treated with alirocumab compared to those treated with evolocumab (RR: 0.84, 95% CI: 0.70-1.00), but the difference was not statistically significant. Conclusions: Alirocumab and evolocumab demonstrated comparable efficacy in reducing the relative risk of major cardiovascular events. The all-cause mortality rates were lower in patients treated with alirocumab compared to those treated with evolocumab but the differences were not statistically significant, probably due to heterogeneity in the sample size and follow-up duration between different studies. Both drugs exhibited comparable safety profiles.
Keywords: Alirocumab, evolocumab, PCSK9 inhibitors, cardiovascular events, efficacy, Safety, Network meta-analysis
Received: 04 Jan 2025; Accepted: 10 Jun 2025.
Copyright: © 2025 Xu, Lei, Li, Li, Zheng and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ping Zheng, Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China
Chunping Gu, Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.