Clinical features modifying the cardiovascular benefits of GLP-1 receptor agonists: a systematic review and meta-analysis.

IF 6.1 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

European Heart Journal - Cardiovascular Pharmacotherapy Pub Date : 2025-09-22 DOI:10.1093/ehjcvp/pvaf037

Arzu Kalayci, James Louis Januzzi, Makiko Mitsunami, Ibrahim Halil Tanboga, Can Yucel Karabay, Charles Michael Gibson

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Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D), but heterogeneity exists across cardiovascular outcome trials (CVOTs). A comprehensive search of PubMed, EMBASE, and Cochrane Library was conducted through November 2024. Eligible CVOTs compared GLP-1 RAs with placebo in T2D patients. The primary outcome was MACE, defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using I², τ², and R². Meta-regression analyses evaluated the influence of baseline covariates on cardiovascular benefits of GLP-1 RAs, contingent upon the detection of moderate to substantial heterogeneity (I² ≥ 30%). Sensitivity analyses and GRADE assessments were also performed. Ten trials (67 769 patients; 34 536 receiving GLP-1 RAs) were analyzed. GLP-1 RAs significantly reduced MACE compared with placebo (OR = 0.87, 95% CI: 0.81-0.93, P < 0.001, I² = 48.4%). Cardiovascular death (OR = 0.86, 95% CI: 0.79-0.94, P < 0.001, I² = 22.6%) and all-cause mortality (OR = 0.87, 95% CI: 0.82-0.94, P < 0.001, I² = 17.7%) were also reduced. Meta-regression revealed a greater cardiovascular benefit in patients with higher baseline body mass index (BMI; logOR = -0.098 per kg/m², P = 0.006, R² = 99.98%) and older age (logOR = -0.033 per year, P = 0.023, R² = 75.47%). Sensitivity analyses confirmed the robustness of these findings, with consistent effect sizes and no single trial unduly influencing the results. The certainty of evidence was rated as high for all outcomes based on GRADE criteria. GLP-1 RAs significantly reduce MACE, cardiovascular death, and all-cause mortality in T2D patients. Higher baseline BMI and older age were associated with greater cardiovascular benefit.

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改变GLP-1受体激动剂心血管益处的临床特征：一项系统回顾和荟萃分析。

胰高血糖素样肽-1受体激动剂（GLP-1 RAs）可减少2型糖尿病（T2D）患者的主要不良心血管事件（MACE），但在心血管结局试验（CVOTs）中存在异质性。对PubMed、EMBASE和Cochrane图书馆进行了全面的检索，直到2024年11月。符合条件的CVOTs比较了T2D患者的GLP-1 RAs与安慰剂。主要终点为MACE，定义为心血管死亡、非致死性心肌梗死和非致死性卒中的综合结果。采用随机效应模型计算95%置信区间（ci）的合并优势比（ORs）。使用I²、τ²和R²评估异质性。meta回归分析评估了基线协变量对GLP-1 RAs心血管益处的影响，这取决于检测到中度至实质性异质性（I²≥30%）。还进行了敏感性分析和GRADE评估。10项试验（67 769例患者，34 536例接受GLP-1 RAs治疗）进行了分析。与安慰剂相比，GLP-1 RAs显著降低了MACE （OR = 0.87, 95% CI: 0.81-0.93, P < 0.001, I²= 48.4%）。心血管死亡率（OR = 0.86, 95% CI: 0.79-0.94, P < 0.001, I²= 22.6%）和全因死亡率（OR = 0.87, 95% CI: 0.82-0.94, P < 0.001, I²= 17.7%）也有所降低。meta回归显示，基线体重指数（BMI; logOR = -0.098 / kg/m²，P = 0.006, R²= 99.98%）较高和年龄较大（logOR = -0.033 /年，P = 0.023, R²= 75.47%）的患者心血管获益更大。敏感性分析证实了这些发现的稳健性，具有一致的效应量，没有单一试验对结果产生不适当的影响。根据GRADE标准，所有结果的证据确定性被评为高。GLP-1 RAs可显著降低T2D患者的MACE、心血管死亡和全因死亡率。基线BMI越高，年龄越大，对心血管的益处越大。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Heart Journal - Cardiovascular Pharmacotherapy Medicine-Cardiology and Cardiovascular Medicine

CiteScore

10.10

自引率

14.10%

发文量

期刊介绍： The European Heart Journal - Cardiovascular Pharmacotherapy (EHJ-CVP) is an international, peer-reviewed journal published in English, specifically dedicated to clinical cardiovascular pharmacology. EHJ-CVP publishes original articles focusing on clinical research involving both new and established drugs and methods, along with meta-analyses and topical reviews. The journal's primary aim is to enhance the pharmacological treatment of patients with cardiovascular disease by interpreting and integrating new scientific developments in this field. While the emphasis is on clinical topics, EHJ-CVP also considers basic research articles from fields such as physiology and molecular biology that contribute to the understanding of cardiovascular drug therapy. These may include articles related to new drug development and evaluation, the physiological and pharmacological basis of drug action, metabolism, drug interactions, and side effects.