AimsGlucagon‐like peptide‐1 receptor agonists reduce major adverse cardiovascular events (MACE) and cardiovascular mortality in people with type 2 diabetes (T2D). However, previous studies suggest the effects on heart failure outcomes vary according to left ventricular ejection fraction (LVEF). We aimed to evaluate the effects of exenatide on cardiovascular events according to LVEF in people with T2D.Methods and resultsPost‐hoc analysis of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial evaluating the effects of once‐weekly exenatide (EQW) versus placebo on cardiovascular outcomes according to baseline LVEF (<40% or ≥40%). Outcomes were also evaluated according to New York Heart Association (NYHA) class and obesity. The main outcome was hospitalization for heart failure (HHF). A treatment‐by‐LVEF interaction was used. In EXSCEL (n = 14 752), 4749 participants had LVEF available at baseline; 455 (10%) with LVEF <40%, 4294 (90%) with LVEF ≥40%. LVEF modified the EQW effect on hHF: hazard ratio (HR) = 1.52 (95% confidence interval [CI] = 0.95–2.43) in participants with LVEF < 40% and HR = 0.74 (95% CI = 0.55–1.01) in those with LVEF ≥ 40% (p‐interaction = 0.012). No significant treatment‐by‐LVEF interactions (p‐interaction >0.10) were observed for MACE, cardiovascular death or all‐cause mortality. The risk of HHF was also modified by baseline NYHA class (HR 0.91, 95% CI 0.65–1.27 for NYHA class I/II; HR 1.84, 95% CI 0.95–3.59 for NYHA class III/IV; p‐interaction = 0.062), mostly driven by the LVEF <40% subgroup. Obesity did not modify the effects of EQW on HHF.ConclusionsThe EQW effect on HHF was influenced by LVEF, with a potentially decreased risk in participants with LVEF ≥40% and increased risk in those with LVEF <40%. The risk of HHF was particularly high in participants with LVEF <40% and NYHA class III/IV. LVEF did not modify the effect of EQW on atherosclerotic outcomes.

中文翻译：

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根据射血分数，艾塞那肽治疗 2 型糖尿病的心血管结局：EXSCEL 试验


Aims胰高血糖素样肽-1 受体激动剂可降低 2 型糖尿病 （T2D） 患者的主要不良心血管事件 （MACE） 和心血管死亡率。然而，先前的研究表明，对心力衰竭结局的影响因左心室射血分数 （LVEF） 而异。我们旨在根据 LVEF 评估艾塞那肽对 T2D 患者心血管事件的影响。方法和结果根据基线 LVEF （<40% 或 ≥40%） 评估每周一次的艾塞那肽降低研究 （EXSCEL） 试验的事后分析，该试验评估了每周一次的艾塞那肽 （EQW） 与安慰剂对心血管结局的影响。还根据纽约心脏协会 （NYHA） 分级和肥胖评估结局。主要结局是因心力衰竭 （HHF） 住院。使用了 LVEF 相互作用治疗。在 EXSCEL （n = 14 752） 中，4749 名参与者在基线时有 LVEF 可用;455 例 （10%） LVEF <40%，4294 例 （90%） LVEF ≥40%。LVEF 改变了 EQW 对 hHF 的影响：LVEF < 40% 和 HR = 0.74 （95% CI = 0.55-1.01） 的参与者的风险比 （HR） = 1.52 （95% 置信区间 [CI] = 0.95-2.43） LVEF ≥ 40% 的参与者 （p 交互作用 = 0.012）。在 MACE、心血管死亡或全因死亡率方面未观察到显着的 LVEF 相互作用治疗 （p 相互作用 >0.10）。基线 NYHA 分级也改变了 HHF 的风险 （NYHA I/II 级 HR 0.91,95% CI 0.65-1.27;NYHA III/IV 级的 HR 1.84,95% CI 0.95-3.59;p 相互作用 = 0.062），主要由 LVEF <40% 亚组驱动。肥胖不会改变 EQW 对 HHF 的影响。结论 EQW 对 HHF 的影响受 LVEF 影响，LVEF ≥40% 参与者的风险可能降低，而 LVEF <40% 的参与者风险增加。 LVEF <40% 和 NYHA III/IV 级的参与者发生 HHF 的风险特别高。LVEF 没有改变 EQW 对动脉粥样硬化结局的影响。