Department of Neurology, Allegheny Health Network, Pittsburgh, PA, USA.
Division of Neurology, McMaster University/Population Health Research Institute, Hamilton, Canada.
J Neurol. 2020 Jul;267(7):2117-2122. doi: 10.1007/s00415-020-09813-4. Epub 2020 Apr 4.
Randomized controlled clinical trials (RCT) have demonstrated varied efficacy of glucagon-like peptide-1 receptor (GLP-1R) agonists for cardiovascular outcomes. We sought to evaluate the efficacy and safety of GLP-1R agonists among patients with Type 2 diabetes mellitus (DM) for stroke prevention.
We conducted a systematic review and meta-analysis of RCTs reporting the following outcomes among patients with Type 2 DM treated with GLP-1R agonists (vs. placebo): nonfatal or fatal strokes, all-cause or cardiovascular mortality, myocardial infarction (MI) and major adverse cardiovascular events (MACE). The protocol of our systematic review and meta-analysis was registered to the PROSPERO database. We pooled odds ratios (OR) using random-effect models, and assessed the heterogeneity using Cochran Q and I statistics.
We identified 8 RCTs, comprising 56,251 patients. In comparison to placebo, GLP-1R agonists reduced nonfatal strokes (OR 0.84; 95% CI 0.76-0.94, p = 0.002; I = 0%) and all strokes (OR 0.84; 95% CI 0.75-0.93, p = 0.001; I = 0%) by 16%. Overall, GLP-1R agonists reduced MACE by 13% (OR 0.87; 95% CI 0.81-0.94, p = 0.0003; I = 42%), cardiovascular mortality by 12% (OR 0.88; 95% CI 0.81-0.95; p = 0.002; I = 0%) and all-cause mortality by 12% (OR 0.88; 95% CI 0.82-0.95, p = 0.0007; I = 15%). Additional analyses demonstrated that GLP-1R agonists reduced the risk of incident MACE (OR 0.86; 95% CI 0.80-0.92; p < 0.0001; I = 0%) among patients with prior history of MI or nonfatal strokes.
Among patients with type 2 DM, GLP-1R agonists are beneficial for primary stroke, MACE, and cardiovascular mortality prevention. Further RCTs are needed to evaluate their role for secondary stroke prevention.
随机对照临床试验（RCT）已证明胰高血糖素样肽-1 受体（GLP-1R）激动剂在心血管结局方面的疗效存在差异。我们旨在评估 2 型糖尿病（T2DM）患者使用 GLP-1R 激动剂预防中风的疗效和安全性。
我们对报告接受 GLP-1R 激动剂（与安慰剂相比）治疗的 T2DM 患者以下结局的 RCT 进行了系统评价和荟萃分析：非致死性或致死性中风、全因或心血管死亡率、心肌梗死（MI）和主要不良心血管事件（MACE）。我们的系统评价和荟萃分析方案已在 PROSPERO 数据库中注册。我们使用随机效应模型汇总比值比（OR），并使用 Cochran Q 和 I 统计量评估异质性。
我们确定了 8 项 RCT，共纳入 56251 名患者。与安慰剂相比，GLP-1R 激动剂可使非致死性中风（OR 0.84；95%CI 0.76-0.94，p=0.002；I=0%）和所有中风（OR 0.84；95%CI 0.75-0.93，p=0.001；I=0%）的风险降低 16%。总体而言，GLP-1R 激动剂使 MACE 减少 13%（OR 0.87；95%CI 0.81-0.94，p=0.0003；I=42%），心血管死亡率降低 12%（OR 0.88；95%CI 0.81-0.95；p=0.002；I=0%），全因死亡率降低 12%（OR 0.88；95%CI 0.82-0.95，p=0.0007；I=15%）。进一步的分析表明，GLP-1R 激动剂可降低有 MI 或非致死性中风既往史患者的 MACE 事件风险（OR 0.86；95%CI 0.80-0.92；p<0.0001；I=0%）。
在 2 型糖尿病患者中，GLP-1R 激动剂有利于预防中风、MACE 和心血管死亡率。需要进一步的 RCT 来评估它们在预防二次中风方面的作用。
