Nauck Michael A, Tornøe Karen, Rasmussen Søren, Treppendahl Marianne Bach, Marso Steven P
1 Diabetes Center Bochum-Hattingen, Medical Department I, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
2 Novo Nordisk A/S, Søborg, Denmark.
Diab Vasc Dis Res. 2018 Sep;15(5):465-468. doi: 10.1177/1479164118783935. Epub 2018 Jun 27.
Animal studies demonstrated that glucagon-like peptide-1 receptor agonists reduce myocardial necrosis following regional ischaemia induction. This effect may improve cardiovascular outcomes after myocardial infarction. Risk of cardiovascular death or hospitalisation for heart failure after myocardial infarction was evaluated in patients with type 2 diabetes at high cardiovascular risk in the LEADER trial.
Data from patients randomised to liraglutide or placebo, in addition to standard of care, in Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) (NCT01179048) were analysed post hoc. Cox regression, with myocardial infarction as a time-dependent covariate, was used to analyse time from randomisation to a composite of cardiovascular death or hospitalisation for heart failure.
Patients who experienced myocardial infarction had a sevenfold higher risk of the composite endpoint (with myocardial infarction: n = 148, 25.0%; without myocardial infarction: n = 716, 8.2%; hazard ratio: 7.0; 95% confidence interval: 5.8, 8.4). The risk of the composite endpoint after myocardial infarction was not significantly lower in the liraglutide group ( n = 63, 23.0%) compared with placebo ( n = 85, 26.7%; hazard ratio: 0.91; 95% confidence interval: 0.66, 1.26).
The data demonstrated that having myocardial infarction significantly increased the risk of subsequent cardiovascular death or hospitalisation for heart failure. However, we did not find evidence for a reduced risk in these cardiovascular outcomes following myocardial infarction in patients treated with liraglutide versus placebo.
动物研究表明,胰高血糖素样肽-1受体激动剂可减少局部缺血诱导后的心肌坏死。这一效应可能改善心肌梗死后的心血管结局。在LEADER试验中,对心血管风险较高的2型糖尿病患者心肌梗死后心血管死亡或因心力衰竭住院的风险进行了评估。
对糖尿病患者使用利拉鲁肽和心血管结局评估(LEADER)试验(NCT01179048)中随机分配至利拉鲁肽或安慰剂组(除标准治疗外)的患者数据进行事后分析。采用以心肌梗死作为时间依赖性协变量的Cox回归分析从随机分组到心血管死亡或因心力衰竭住院这一复合终点的时间。
发生心肌梗死的患者出现复合终点的风险高出7倍(发生心肌梗死:n = 148,25.0%;未发生心肌梗死:n = 716,8.2%;风险比:7.0;95%置信区间:5.8,8.4)。与安慰剂组(n = 85,26.7%;风险比:0.91;95%置信区间:0.66,1.26)相比,利拉鲁肽组心肌梗死后复合终点的风险并未显著降低(n = 63,23.0%)。
数据表明,发生心肌梗死会显著增加随后心血管死亡或因心力衰竭住院的风险。然而,我们未发现证据表明,与安慰剂相比,利拉鲁肽治疗的患者心肌梗死后这些心血管结局的风险有所降低。