GLP-1受体激动剂的心血管效应和耐受性:99,592例患者的系统回顾和荟萃分析

IF 22.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Mattia Galli, Stefano Benenati, Claudio Laudani, Beatrice Simeone, Gianmarco Sarto, Luis Ortega-Paz, Erica Rocco, Marco Bernardi, Luigi Spadafora, Domenico D'Amario, Ernesto Greco, Giacomo Frati, Massimo Federici, Roxana Mehran, Filippo Crea, Dominick J Angiolillo, Sebastiano Sciarretta
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引用次数: 0

摘要

背景:胰高血糖素样肽-1受体激动剂(GLP-1 RAs)已显示出显著的心血管(CV)益处,特别是在糖尿病(DM)患者中,但不同GLP-1 RAs在不同人群中的安全性和有效性仍未充分确定。目的:以往GLP-1 RAs的荟萃分析受到人群限制、近期试验的遗漏或不完整的安全性合成的限制;本研究采用先进的荟萃分析方法整合了21项随机对照试验和不同人群的最新证据。方法:纳入比较GLP-1 RAs与对照组或安慰剂的随机对照试验。根据使用的GLP-1 RA进行预先指定的亚组分析。根据糖尿病、肾功能、肥胖或心力衰竭(HF)进行预先指定的亚组。主要结局包括死亡率(全因和CV)、试验定义的主要不良心血管事件(MACE)和严重不良事件(SAEs)。分别进行GRADE和试验序列分析来评估结果的确定性和结论性。结果:共纳入21项试验,共99,592例患者。使用了8种不同的GLP-1 RAs(利昔那肽、利拉鲁肽、艾塞那肽、西马鲁肽、依佩格莱肽、杜拉鲁肽、阿比鲁肽和替西帕肽),每种都以治疗剂量给药,并与安慰剂或对照组进行比较。平均随访时间为2.4年。我们发现了确凿的、高确定性的证据,与对照组相比,GLP-1 RAs降低了全因死亡(IRR 0.88, 95% CI 0.84-0.92, NNT=121)、CV死亡(IRR 0.87, 95% CI 0.81-0.92, NNT=170)和MACE (IRR 0.87, 95% CI 0.83-0.91, NNT=66)。GLP-1 RAs降低了SAE(-9%)、心肌梗死(-15%)、急性肾衰竭(-9%)、HF(-15%)和感染(-10%),但增加了胃肠道(+ 63%)和胆囊(+26%)疾病。在中风、胰腺炎和肿瘤方面,两组间没有差异。各亚组的结果基本一致。GLP-1 RA型分析揭示了疗效和安全性的潜在差异。结论:GLP-1 RAs降低了高危人群的死亡率和MACE,突出了血糖控制以外的益处。这些会增加胃肠道和胆囊的风险。疗效和耐受性的差异支持根据个体患者特征和治疗目标定制GLP-1 RA治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of 99,599 Patients.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant cardiovascular (CV) benefits, particularly in patients with diabetes mellitus, but the safety and efficacy of different GLP-1 RAs across diverse populations remain insufficiently defined.

Objectives: Previous meta-analyses of GLP-1 RAs have been limited by restricted populations, omission of recent trials, or incomplete safety synthesis; this study integrates the latest evidence across 21 randomized controlled trials and diverse populations using advanced meta-analytic methods.

Methods: Randomized controlled trials comparing GLP-1 RAs vs controls or placebo were included. Analyses were conducted in prespecified subgroups based on the GLP-1 RA used. Prespecified subgroups according to diabetes mellitus, kidney function, obesity, or heart failure were also performed. Main outcomes comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events. GRADE (Grading of Recommendations Assessment, Development and Evaluation) and trial sequential analyses were performed to evaluate certainty and conclusiveness of findings, respectively.

Results: A total of 21 trials encompassing 99,599 patients were included. Eight different GLP-1 RAs were used (lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide), each administered at therapeutic doses and compared vs placebo or controls. Mean follow-up duration was 2.4 years. We found conclusive, high-certainty evidence that GLP-1 RAs reduced all-cause death (incidence rate ratio [IRR]: 0.88; 95% CI: 0.84-0.92; needed to treat [NNT] = 121), CV death (IRR: 0.87; 95% CI: 0.81-0.92; NNT = 170), and MACE (IRR: 0.87; 95% CI: 0.83-0.91; NNT = 66), compared with controls. GLP-1 RAs reduced serious adverse events (-9%), myocardial infarction (-15%), acute kidney failure (-9%), heart failure (-15%), and infections (-10%), but increased gastrointestinal (+63%) and gallbladder (+26%) disorders. There were no differences in stroke, pancreatitis, or neoplasm between groups. Results were mostly consistent across subgroups. Analysis by GLP-1 RA type revealed potential differences in efficacy and safety profiles.

Conclusions: GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control. These come at increased gastrointestinal and gallbladder risks. Variation in efficacy and tolerability supports tailoring GLP-1 RA therapy to individual patient characteristics and treatment goals. (PROSPERO [GLP-1 RAs Reduce Mortality and Cardiovascular Events Across the Spectrum of Treated Patients: A Systematic Review and Meta-Analysis; CRD420251032222]).

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来源期刊
CiteScore
42.70
自引率
3.30%
发文量
5097
审稿时长
2-4 weeks
期刊介绍: The Journal of the American College of Cardiology (JACC) publishes peer-reviewed articles highlighting all aspects of cardiovascular disease, including original clinical studies, experimental investigations with clear clinical relevance, state-of-the-art papers and viewpoints. Content Profile: -Original Investigations -JACC State-of-the-Art Reviews -JACC Review Topics of the Week -Guidelines & Clinical Documents -JACC Guideline Comparisons -JACC Scientific Expert Panels -Cardiovascular Medicine & Society -Editorial Comments (accompanying every Original Investigation) -Research Letters -Fellows-in-Training/Early Career Professional Pages -Editor’s Pages from the Editor-in-Chief or other invited thought leaders
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