GLP-1RA versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: An updated meta-analysis of randomized controlled trials

IF 3.2 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

International journal of cardiology Pub Date : 2025-07-05 DOI:10.1016/j.ijcard.2025.133604

Sanchit Duhan , Krishna Prasad Kurpad , Bijeta Keisham , Jurgen Shtembari , Alina Brener , Uday B. Kanakadandi , Anuj Garg , Naveed A. Adoni , Sanjay S. Mehta

{"title":"GLP-1RA versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: An updated meta-analysis of randomized controlled trials","authors":"Sanchit Duhan , Krishna Prasad Kurpad , Bijeta Keisham , Jurgen Shtembari , Alina Brener , Uday B. Kanakadandi , Anuj Garg , Naveed A. Adoni , Sanjay S. Mehta","doi":"10.1016/j.ijcard.2025.133604","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Currently, limited guideline-directed medical therapies are available for heart failure (HF) with preserved and mildly reduced ejection fraction (EF). Both are associated with an increased risk of hospitalization and death, especially in overweight, obese, or diabetic individuals.</div></div><div><h3>Methods</h3><div>We searched Cochrane, Embase, and MEDLINE from inception to November 2024. Trials with HF patients randomized for GLP-1RA (glucagon-like peptide-1 receptor agonists) and reported adverse cardiovascular and mortality outcomes were included. Statistical analysis was performed using Cochrane Review Manager 5.4.1.</div></div><div><h3>Results</h3><div>4474 patients with HF (preserved and mildly reduced EF) were included in the study. 2278 (50.91 %) received a GLP-1RA [either semaglutide (1914, 84 %) or Tirzepatide (364, 16 %)], and 2196 (49.01 %) received a placebo. GLP-1RA reduced the composite event of cardiovascular mortality and worsening HF exacerbation [139 vs. 194, RR: 0.64 (95 % CI: 0.45–0.92)]. However, on subgroup analysis, there was no significant difference in cardiovascular (CV) deaths [67 vs. 71, RR 0.89 (95 % CI: 0.65–1.24)]. The HF exacerbations were significantly reduced in the GLP-1RA group [83 vs. 138, RR 0.59 (95 % CI: 0.45–0.76)]. Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) was favorable for GLP-1RA [Std Mean Difference (SMD): 7.38 (95 % CI: 5.51–9.26)], reflected by an increase in 6-min walk distance in GLP-1RA groups [SMD: 17.69 (95 % CI: 11.87–23.34)] and contributed by a decrease in body weight in GLP-1RA groups [SMD -9.56 (95 % CI -12.74 to −6.39)].</div></div><div><h3>Conclusion</h3><div>GLP-1RA reduce HF exacerbations and can play a role in reducing hospitalizations, improving patient's functional status, and significantly impacting the global healthcare burden of HF. However, the current data does not indicate any overall mortality benefit.</div></div>","PeriodicalId":13710,"journal":{"name":"International journal of cardiology","volume":"438 ","pages":"Article 133604"},"PeriodicalIF":3.2000,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of cardiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167527325006473","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction

Currently, limited guideline-directed medical therapies are available for heart failure (HF) with preserved and mildly reduced ejection fraction (EF). Both are associated with an increased risk of hospitalization and death, especially in overweight, obese, or diabetic individuals.

Methods

We searched Cochrane, Embase, and MEDLINE from inception to November 2024. Trials with HF patients randomized for GLP-1RA (glucagon-like peptide-1 receptor agonists) and reported adverse cardiovascular and mortality outcomes were included. Statistical analysis was performed using Cochrane Review Manager 5.4.1.

Results

4474 patients with HF (preserved and mildly reduced EF) were included in the study. 2278 (50.91 %) received a GLP-1RA [either semaglutide (1914, 84 %) or Tirzepatide (364, 16 %)], and 2196 (49.01 %) received a placebo. GLP-1RA reduced the composite event of cardiovascular mortality and worsening HF exacerbation [139 vs. 194, RR: 0.64 (95 % CI: 0.45–0.92)]. However, on subgroup analysis, there was no significant difference in cardiovascular (CV) deaths [67 vs. 71, RR 0.89 (95 % CI: 0.65–1.24)]. The HF exacerbations were significantly reduced in the GLP-1RA group [83 vs. 138, RR 0.59 (95 % CI: 0.45–0.76)]. Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) was favorable for GLP-1RA [Std Mean Difference (SMD): 7.38 (95 % CI: 5.51–9.26)], reflected by an increase in 6-min walk distance in GLP-1RA groups [SMD: 17.69 (95 % CI: 11.87–23.34)] and contributed by a decrease in body weight in GLP-1RA groups [SMD -9.56 (95 % CI -12.74 to −6.39)].

Conclusion

GLP-1RA reduce HF exacerbations and can play a role in reducing hospitalizations, improving patient's functional status, and significantly impacting the global healthcare burden of HF. However, the current data does not indicate any overall mortality benefit.

Abstract Image

查看原文本刊更多论文

GLP-1RA与安慰剂在心力衰竭患者和轻度降低或保留射血分数：随机对照试验的最新荟萃分析

目前，有限的指导药物治疗可用于心力衰竭（HF）保留和轻度降低射血分数（EF）。两者都与住院和死亡风险增加有关，尤其是超重、肥胖或糖尿病患者。方法检索Cochrane、Embase和MEDLINE自成立至2024年11月。纳入了随机使用GLP-1RA（胰高血糖素样肽-1受体激动剂）的HF患者的试验，并报告了不良的心血管和死亡率结果。采用Cochrane Review Manager 5.4.1进行统计分析。结果4474例HF患者（保留的EF和轻度减少的EF）纳入研究。2278人（50.91%）接受GLP-1RA治疗[西马鲁肽（1914,84%）或替西帕肽（364,16%）]，2196人（49.01%）接受安慰剂治疗。GLP-1RA降低心血管死亡率和心衰加重的复合事件[139 vs. 194, RR: 0.64 (95% CI: 0.45-0.92)]。然而，在亚组分析中，心血管（CV）死亡率无显著差异[67比71，RR 0.89 (95% CI: 0.65-1.24)]。GLP-1RA组心衰加重明显减少[83比138，RR 0.59 (95% CI: 0.45-0.76)]。堪萨斯城心肌病问卷临床总结评分（KCCQ-CSS）对GLP-1RA有利[标准平均差值（SMD）： 7.38 (95% CI: 5.51-9.26)]，反映在GLP-1RA组6分钟步行距离的增加[SMD: 17.69 (95% CI: 11.87-23.34)]和GLP-1RA组体重的下降[SMD -9.56 (95% CI: -12.74至- 6.39)]。结论lp - 1ra可减少心衰加重，降低住院率，改善患者功能状态，显著影响全球心衰医疗负担。然而，目前的数据并没有显示任何总体的死亡率益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

International journal of cardiology 医学-心血管系统

CiteScore

6.80

自引率

5.70%

发文量

758

审稿时长

44 days

期刊介绍： The International Journal of Cardiology is devoted to cardiology in the broadest sense. Both basic research and clinical papers can be submitted. The journal serves the interest of both practicing clinicians and researchers. In addition to original papers, we are launching a range of new manuscript types, including Consensus and Position Papers, Systematic Reviews, Meta-analyses, and Short communications. Case reports are no longer acceptable. Controversial techniques, issues on health policy and social medicine are discussed and serve as useful tools for encouraging debate.