Siddiqi Tariq Jamal, Khan Muhammad Shahzeb, Waqas Saad Ahmed, Van Spall Harriette G C, Shapiro Michael D, Fonarow Gregg C, Januzzi James L, Afzal Aasim M, Pandey Ambarish, Butler Javed, Greene Stephen J
Department of Internal Medicine, Baylor University Medical Center, Dallas, TX, USA.
Baylor College of Medicine, Temple, TX, USA.
Eur J Heart Fail. 2025 Dec;27(12):2844-2854. doi: 10.1002/ejhf.70048. Epub 2025 Sep 22.
Effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart failure hospitalization (HFH) and cardiovascular (CV) death among patients with varying overlap of cardiovascular-kidney-metabolic (CKM) comorbidity are not well characterized. This study aimed to assess effects GLP-1RAs on HFH and CV death across populations with varying type and number of CKM comorbidity.
Online databases were queried through November 2024 for primary and secondary analyses of clinical outcome trials of GLP-1RAs in patients with heart failure (HF), type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), obesity, and combinations of these diseases. Primary outcome was a composite HFH or CV death. Secondary outcomes were first HFH and CV death. Hazard ratios (HRs), risk ratios (RRs), and their 95% confidence intervals (CI) were derived using random-effects models. Fifteen trials (n = 87 549) were included. Compared with placebo, GLP-1RAs reduced the relative risk of composite HFH/CV death in HF (HR 0.81, 95% CI 0.69-0.96), T2DM (HR 0.85, 95% CI 0.78-0.93), and obesity (HR 0.70, 95% CI 0.58-0.86), with a non-significant risk reduction in CKD (HR 0.79, 95% CI 0.61-1.01). GLP-1RAs reduced the risk of HFH in T2DM (HR 0.89, 95% CI 0.80-0.99) and obesity (HR 0.63, 95% CI 0.45-0.87), with a non-significant risk reduction among patients with HF (HR 0.85, 95% CI 0.69-1.04) and CKD (HR 0.82, 95% CI 0.64-1.06). GLP-1RAs also significantly reduced CV death in HF (HR 0.88, 95% CI 0.77-0.99), T2DM (HR 0.85, 95% CI 0.78-0.93), and in obesity (HR 0.83, 95% CI 0.73-0.93), with a non-significant risk reduction in CKD (HR 0.80, 95% CI 0.60-1.08). Effects were consistent across subgroups, except for HF with reduced ejection fraction (HFrEF), where GLP-1RAs showed a non-significant risk increase in HFH (HR 1.17, 95% CI 0.93-1.47) but significantly reduced CV death (HR 0.67, 95% CI 0.50-0.90). GLP-1RAs were not associated with increased risk for serious adverse events (RR 0.94, 95% CI 0.89-1.00).
Glucagon-like peptide-1 receptor agonists reduce HFH and CV death across CKM conditions, with generally consistent effects in varying combinations of these diseases. The potential exception is among patients with HFrEF, where a reduction in risk of CV death, but a numeric increase in HFH, was observed. Definitive CV outcome trials are needed to definitively determine effects of GLP-1RAs in patients with established HFrEF.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）对心血管-肾脏-代谢（CKM）合并症不同重叠情况的患者发生心力衰竭住院（HFH）及心血管（CV）死亡的影响尚未得到充分描述。本研究旨在评估GLP-1RAs对不同类型和数量CKM合并症患者的HFH及CV死亡的影响。
检索在线数据库至2024年11月，以对GLP-1RAs在心力衰竭（HF）、2型糖尿病（T2DM）、慢性肾脏病（CKD）、肥胖症以及这些疾病组合患者中的临床结局试验进行一级和二级分析。主要结局为HFH或CV死亡的复合终点。次要结局为首次HFH和CV死亡。采用随机效应模型得出风险比（HRs）、风险率（RRs）及其95%置信区间（CI）。纳入了15项试验（n = 87549）。与安慰剂相比，GLP-1RAs降低了HF（HR 0.81，95%CI 0.69 - 0.96）、T2DM（HR 0.85，95%CI 0.78 - 0.93）和肥胖症（HR 0.70，95%CI 0.58 - 0.86）患者复合HFH/CV死亡的相对风险，CKD患者风险降低不显著（HR 0.79，95%CI 0.61 - 1.01）。GLP-1RAs降低了T2DM（HR 0.89，95%CI 0.80 - 0.99）和肥胖症（HR 0.63，95%CI 0.45 - 0.87）患者的HFH风险，HF（HR 0.85，95%CI 0.69 - 1.04）和CKD（HR 0.82，95%CI 0.64 - 1.06）患者风险降低不显著。GLP-1RAs还显著降低了HF（HR 0.88，95%CI 0.77 - 0.99）、T2DM（HR 0.85，95%CI 0.78 - 0.93）和肥胖症（HR 0.83，95%CI 0.73 - 0.93）患者的CV死亡风险，CKD患者风险降低不显著（HR 0.80，95%CI 0.60 - 1.08）。除射血分数降低的心力衰竭（HFrEF）患者外，各亚组的效应均一致，在HFrEF患者中，GLP-1RAs使HFH风险增加但不显著（HR 1.17，95%CI 0.93 - 1.47），但显著降低了CV死亡风险（HR 0.67，95%CI 0.50 - 0.90）。GLP-1RAs与严重不良事件风险增加无关（RR 0.94，95%CI 0.89 - 1.00）。
胰高血糖素样肽-1受体激动剂可降低CKM情况下的HFH及CV死亡风险，在这些疾病的不同组合中效应总体一致。潜在的例外是HFrEF患者，在该组中观察到CV死亡风险降低，但HFH在数值上有所增加。需要进行确定性的心血管结局试验来明确GLP-1RAs对已确诊HFrEF患者的影响。
