Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysis

BackgroundAlirocumab 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 com...

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Main Authors: Leyu Xu, Ming Lei, Liren Li, Yilei Li, Chunping Gu, Ping Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1555508/full
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author Leyu Xu
Leyu Xu
Ming Lei
Ming Lei
Liren Li
Liren Li
Yilei Li
Yilei Li
Chunping Gu
Chunping Gu
Ping Zheng
Ping Zheng
author_facet Leyu Xu
Leyu Xu
Ming Lei
Ming Lei
Liren Li
Liren Li
Yilei Li
Yilei Li
Chunping Gu
Chunping Gu
Ping Zheng
Ping Zheng
author_sort Leyu Xu
collection DOAJ
description BackgroundAlirocumab 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.MethodsPUBMED, 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 17 August 2024. The meta-analysis was performed using Software Review Manager 5.4 and R 4.1.0 software.ResultsThis network meta-analysis included 26 RCTs with 64,921 patients. Among these, 13 RCTs included patients receiving alirocumab or placebo (n = 13,365) and 13 RCTs included patients receiving evolocumab or placebo (n = 22,048). 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.ConclusionAlirocumab 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.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD42024505327.
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spelling doaj-art-5ed56d04f72c40dd9874a50a3f75f3eb2025-08-20T03:29:22ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15555081555508Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysisLeyu Xu0Leyu Xu1Ming Lei2Ming Lei3Liren Li4Liren Li5Yilei Li6Yilei Li7Chunping Gu8Chunping Gu9Ping Zheng10Ping Zheng11Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaClinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaBackgroundAlirocumab 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.MethodsPUBMED, 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 17 August 2024. The meta-analysis was performed using Software Review Manager 5.4 and R 4.1.0 software.ResultsThis network meta-analysis included 26 RCTs with 64,921 patients. Among these, 13 RCTs included patients receiving alirocumab or placebo (n = 13,365) and 13 RCTs included patients receiving evolocumab or placebo (n = 22,048). 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.ConclusionAlirocumab 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.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD42024505327.https://www.frontiersin.org/articles/10.3389/fphar.2025.1555508/fullalirocumabevolocumabPCSK9 inhibitorscardiovascular eventsefficacysafety
spellingShingle Leyu Xu
Leyu Xu
Ming Lei
Ming Lei
Liren Li
Liren Li
Yilei Li
Yilei Li
Chunping Gu
Chunping Gu
Ping Zheng
Ping Zheng
Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysis
Frontiers in Pharmacology
alirocumab
evolocumab
PCSK9 inhibitors
cardiovascular events
efficacy
safety
title Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysis
title_full Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysis
title_fullStr Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysis
title_full_unstemmed Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysis
title_short Indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events: a systematic review and network meta-analysis
title_sort indirect comparison of the efficacy and safety of alirocumab and evolocumab on major cardiovascular events a systematic review and network meta analysis
topic alirocumab
evolocumab
PCSK9 inhibitors
cardiovascular events
efficacy
safety
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1555508/full
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