Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis

Background: Direct comparisons between the drugs are limited, and the dosing remains debatable. Therefore, the study aims to indirectly compare the efficacy and safety of inclisiran, alirocumab, evolocumab, and evinacumab in lipid-lowering through a network meta-analysis....

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Main Authors: Lin Zhang, Bin Li, Wei Chen, Wei Li, Huayun Yang, Diguang Pan
Format: Article
Language:English
Published: IMR Press 2025-02-01
Series:Reviews in Cardiovascular Medicine
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Online Access:https://www.imrpress.com/journal/RCM/26/2/10.31083/RCM25248
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author Lin Zhang
Bin Li
Wei Chen
Wei Li
Huayun Yang
Diguang Pan
author_facet Lin Zhang
Bin Li
Wei Chen
Wei Li
Huayun Yang
Diguang Pan
author_sort Lin Zhang
collection DOAJ
description Background: Direct comparisons between the drugs are limited, and the dosing remains debatable. Therefore, the study aims to indirectly compare the efficacy and safety of inclisiran, alirocumab, evolocumab, and evinacumab in lipid-lowering through a network meta-analysis. Methods: Databases including PubMed, EMBASE, Web of Science, and the Cochrane Library were utilized to retrieve randomized controlled trials (RCTs). The search was conducted up to July 1, 2023. The Cochrane risk of bias tool was employed to appraise the quality of included studies. R software was used to conduct the Bayesian network meta-analysis. Results: Twenty-one RCTs with 10,835 patients were included. The network meta-analysis indicated that Evolocumab [mean difference (MD) = –60, 95% credibility interval (CrI) (–72, –49)] was the most effective (87%) in reducing low-density lipoprotein cholesterol (LDL-C), followed by alirocumab (71.4%) and inclisiran (47.2%), with placebo being the least effective (0.01%). In increasing high-density lipoprotein cholesterol (HDL-C), evolocumab [MD = 6.5, 95% CrI (3.2, 10)] ranked first (81.8%), followed by alirocumab (68.2%), with placebo again at the bottom (0.03%). In lowering total cholesterol, evolocumab [MD = –36, 95% CrI (–54, –19)] performed the best (86%), followed by alirocumab (64%), and placebo remained the least effective (0.04%). Regarding adverse events (AEs), evinacumab [odds ratio (OR) = 2, 95% CrI (1.17, 3.44)] ranked the highest (98.9%), followed by inclisiran (59.6%) and evolocumab (15.2%). Conclusions: Evolocumab appears to be the most effective in increasing HDL-C and reducing LDL-C and total cholesterol. Evinacumab shows the best safety profile with the lowest incidence of AEs. The PROSPERO registration: CRD42024570445, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=570445.
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series Reviews in Cardiovascular Medicine
spelling doaj-art-ce54cd8b157e44d98a4cfb8262914f412025-08-20T02:11:13ZengIMR PressReviews in Cardiovascular Medicine1530-65502025-02-012622524810.31083/RCM25248S1530-6550(24)01618-1Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-AnalysisLin Zhang0Bin Li1Wei Chen2Wei Li3Huayun Yang4Diguang Pan5Department of Cardiology, Guilin People’s Hospital, 541002 Guilin, Guangxi, ChinaDepartment of Cardiology, Guilin People’s Hospital, 541002 Guilin, Guangxi, ChinaDepartment of Cardiology, Guilin People’s Hospital, 541002 Guilin, Guangxi, ChinaDepartment of Cardiology, Guilin People’s Hospital, 541002 Guilin, Guangxi, ChinaDepartment of Cardiology, Guilin People’s Hospital, 541002 Guilin, Guangxi, ChinaDepartment of Cardiology, Guilin People’s Hospital, 541002 Guilin, Guangxi, ChinaBackground: Direct comparisons between the drugs are limited, and the dosing remains debatable. Therefore, the study aims to indirectly compare the efficacy and safety of inclisiran, alirocumab, evolocumab, and evinacumab in lipid-lowering through a network meta-analysis. Methods: Databases including PubMed, EMBASE, Web of Science, and the Cochrane Library were utilized to retrieve randomized controlled trials (RCTs). The search was conducted up to July 1, 2023. The Cochrane risk of bias tool was employed to appraise the quality of included studies. R software was used to conduct the Bayesian network meta-analysis. Results: Twenty-one RCTs with 10,835 patients were included. The network meta-analysis indicated that Evolocumab [mean difference (MD) = –60, 95% credibility interval (CrI) (–72, –49)] was the most effective (87%) in reducing low-density lipoprotein cholesterol (LDL-C), followed by alirocumab (71.4%) and inclisiran (47.2%), with placebo being the least effective (0.01%). In increasing high-density lipoprotein cholesterol (HDL-C), evolocumab [MD = 6.5, 95% CrI (3.2, 10)] ranked first (81.8%), followed by alirocumab (68.2%), with placebo again at the bottom (0.03%). In lowering total cholesterol, evolocumab [MD = –36, 95% CrI (–54, –19)] performed the best (86%), followed by alirocumab (64%), and placebo remained the least effective (0.04%). Regarding adverse events (AEs), evinacumab [odds ratio (OR) = 2, 95% CrI (1.17, 3.44)] ranked the highest (98.9%), followed by inclisiran (59.6%) and evolocumab (15.2%). Conclusions: Evolocumab appears to be the most effective in increasing HDL-C and reducing LDL-C and total cholesterol. Evinacumab shows the best safety profile with the lowest incidence of AEs. The PROSPERO registration: CRD42024570445, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=570445.https://www.imrpress.com/journal/RCM/26/2/10.31083/RCM25248total cholesterollow density lipoprotein cholesterinhigh density lipoprotein
spellingShingle Lin Zhang
Bin Li
Wei Chen
Wei Li
Huayun Yang
Diguang Pan
Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis
Reviews in Cardiovascular Medicine
total cholesterol
low density lipoprotein cholesterin
high density lipoprotein
title Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis
title_full Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis
title_fullStr Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis
title_full_unstemmed Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis
title_short Effects of Inclisiran, Alirocumab, Evolocumab, and Evinacumab on Lipids: A Network Meta-Analysis
title_sort effects of inclisiran alirocumab evolocumab and evinacumab on lipids a network meta analysis
topic total cholesterol
low density lipoprotein cholesterin
high density lipoprotein
url https://www.imrpress.com/journal/RCM/26/2/10.31083/RCM25248
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