利拉鲁肽对伴有或不伴有心力衰竭的糖尿病患者心血管结局的影响。
Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure.
机构信息
Midwest Heart and Vascular Institute, HCA Midwest Health, Overland Park, Kansas.
Novo Nordisk A/S, Søborg, Denmark.
出版信息
J Am Coll Cardiol. 2020 Mar 17;75(10):1128-1141. doi: 10.1016/j.jacc.2019.12.063.
BACKGROUND
More data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required.
OBJECTIVES
The purpose of this study was to investigate the effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history.
METHODS
In the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted.
RESULTS
At baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio [HR]: 0.81 [95% confidence interval (CI): 0.65 to 1.02]) and without (HR: 0.88 [95% CI: 0.78 to 1.00]) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 [95% CI: 0.70 to 1.14] with HF; HR: 0.83 [95% CI: 0.70 to 0.97] without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 [95% CI: 0.75 to 1.28] with HF; HR: 0.78 [95% CI: 0.61 to 1.00] without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 [95% CI: 0.74 to 1.15]) and without (HR: 0.77 [95% CI: 0.65 to 0.91]) a history of HF (p interaction = 0.19).
CONCLUSIONS
Based on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]; NCT01179048).
背景
需要更多关于胰高血糖素样肽-1 受体激动剂在 2 型糖尿病（T2D）和心力衰竭（HF）患者中的作用的数据。
目的
本研究旨在通过 HF 病史，探讨利拉鲁肽对 LEADER（Liraglutide Effect and Action in Diabetes：Evaluation of Cardiovascular Outcome Results）参与者心血管事件和死亡率的影响。
方法
在这项多中心、双盲、随机 LEADER 试验中，9340 名 T2D 合并高心血管风险患者按 1:1 随机分配至利拉鲁肽（1.8mg 每日或最大耐受剂量至 1.8mg 每日）或安慰剂加标准治疗组，并随访 3.5 至 5 年。纽约心脏协会（NYHA）心功能 IV 级 HF 为排除标准。主要复合主要不良心血管事件结局为首次发生心血管死亡、非致死性心肌梗死或非致死性卒中的时间。对基线 HF 病史的结局进行了事后 Cox 回归分析。
结果
基线时，18%的患者有 NYHA 心功能 I 至 III 级 HF 病史（利拉鲁肽：n=4668 中的 835；安慰剂：n=4672 中的 832）。利拉鲁肽与安慰剂相比，在有（风险比[HR]：0.81[95%置信区间（CI）：0.65 至 1.02]）和无（HR：0.88[95%CI：0.78 至 1.00]）HF 病史的患者中，对主要不良心血管事件的影响一致（p 交互=0.53）。在这两个亚组中，利拉鲁肽组死亡人数均较少（HR：0.89[95%CI：0.70 至 1.14]有 HF；HR：0.83[95%CI：0.70 至 0.97]无 HF；p 交互=0.63）。与安慰剂相比，利拉鲁肽并未增加 HF 住院风险，无论是否存在 HF 病史（HR：0.98[95%CI：0.75 至 1.28]有 HF；HR：0.78[95%CI：0.61 至 1.00]无 HF；p 交互=0.22）。利拉鲁肽对 HF 住院或心血管死亡复合结局的影响在有（HR：0.92[95%CI：0.74 至 1.15]）和无（HR：0.77[95%CI：0.65 至 0.91]）HF 病史的患者中一致（p 交互=0.19）。
结论
基于这些发现，利拉鲁肽可考虑适用于有或无 NYHA 心功能 I 至 III 级 HF 病史的 T2D 患者。（Liraglutide Effect and Action in Diabetes：Evaluation of Cardiovascular Outcome Results [LEADER]；NCT01179048）。
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