Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal.
Université de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithématique 14-33, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.
Eur J Heart Fail. 2022 Oct;24(10):1792-1801. doi: 10.1002/ejhf.2660. Epub 2022 Sep 9.
Glucagon-like peptide-1 receptor agonists (GLP1-RA) improve cardiovascular outcomes in patients with type 2 diabetes (T2D). However, some studies suggest that their effects in patients with heart failure (HF) may be attenuated. We aimed to explore the effects of the GLP1-RA albiglutide on HF outcomes in patients with and without HF history enrolled in the Harmony Outcomes trial.
Harmony Outcomes enrolled patients with T2D and cardiovascular disease randomized to either albiglutide or placebo over a median follow-up of 1.6 years. A total of 9462 patients were included, of whom 1922 (20%) had HF history. Patients with HF had more cardiovascular comorbidities, poorer renal function, and had a three to four-fold higher risk of HF events compared to patients without HF. Compared to placebo, the effect of albiglutide on the composite of cardiovascular death or HF hospitalization was more pronounced among patients without HF (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.95) than in patients with HF (HR 1.06, 95% CI 0.79-1.43) (interaction p = 0.062). A similar pattern was observed for HF hospitalizations (interaction p = 0.025). The effect of albiglutide on cardiovascular death, sudden death or 'pump failure' death, and all-cause mortality was also attenuated among patients with HF history, but without significant interaction (p > 0.1). The benefit of albiglutide to reduce atherosclerotic events was consistent regardless of HF history.
In patients with T2D and cardiovascular disease, albiglutide appeared to have no effect in reducing HF-related events among patients with HF history. These findings, placed in the context of other trials, suggest that GLP1-RA may not improve HF outcomes in patients with HF.
胰高血糖素样肽-1 受体激动剂（GLP1-RA）可改善 2 型糖尿病（T2D）患者的心血管结局。然而，一些研究表明，它们在心力衰竭（HF）患者中的作用可能会减弱。我们旨在探讨 GLP1-RA 阿必鲁肽对参加 Harmony Outcomes 试验的有和无 HF 病史的 T2D 患者 HF 结局的影响。
Harmony Outcomes 试验纳入了 T2D 合并心血管疾病的患者，随机分为阿必鲁肽或安慰剂组，中位随访 1.6 年。共纳入 9462 例患者，其中 1922 例（20%）有 HF 病史。HF 患者有更多的心血管合并症、更差的肾功能，HF 事件的风险比无 HF 患者高 3 至 4 倍。与安慰剂相比，阿必鲁肽对无 HF 患者心血管死亡或 HF 住院的复合终点的影响更为显著（风险比 [HR] 0.73，95%置信区间 [CI] 0.56-0.95），而在 HF 患者中则不显著（HR 1.06，95%CI 0.79-1.43）（交互作用 p=0.062）。HF 住院的结果也类似（交互作用 p=0.025）。阿必鲁肽对心血管死亡、猝死或“泵衰竭”死亡以及全因死亡率的影响在有 HF 病史但无 HF 的患者中也减弱，但无显著交互作用（p>0.1）。阿必鲁肽减少动脉粥样硬化事件的益处与 HF 病史无关。
在 T2D 合并心血管疾病的患者中，阿必鲁肽似乎对有 HF 病史的患者不能减少 HF 相关事件。这些发现结合其他试验表明，GLP1-RA 可能不能改善 HF 患者的 HF 结局。
