利西拉肽治疗 2 型糖尿病合并急性冠状动脉综合征患者的疗效。
Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.
机构信息
From the Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School - both in Boston (M.A.P., B.C., E.F.L., S.D.S.); Estudios Clínicos Latinoamérica, Rosario, Argentina (R.D.); University of Bergen, Stavanger University Hospital, Stavanger, Norway (K.D.); McMaster University, Hamilton, ON, Canada (H.C.G.); Rigshospitalet Copenhagen University Hospital, Copenhagen (L.V.K.); Sanofi U.S., Bridgewater, NJ (F.C.L., L.P., X.W.); Research Center of the Italian Association of Hospital Cardiologists, Florence (A.P.M.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M.); University of Washington Medical Center, Seattle (J.L.P.); Oregon Health and Science University, Portland (M.C.R.); and Montreal Heart Institute, Université de Montréal, Montreal (J.C.T.).
出版信息
N Engl J Med. 2015 Dec 3;373(23):2247-57. doi: 10.1056/NEJMoa1509225.
BACKGROUND
Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.
METHODS
We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.
RESULTS
The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo.
CONCLUSIONS
In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).
背景
2 型糖尿病患者的心血管发病率和死亡率高于大多数其他人群，尤其是那些同时患有心血管疾病的患者。我们评估了胰高血糖素样肽 1 受体激动剂利西那肽在近期发生急性冠状动脉事件的 2 型糖尿病患者中的心血管结局的影响。
方法
我们将近期发生心肌梗死或在过去 180 天内因不稳定型心绞痛住院的 2 型糖尿病患者随机分为接受利西那肽或安慰剂联合当地确定的标准治疗的两组。该试验的设计具有足够的统计学效力，以评估利西那肽是否不仅不劣于安慰剂（定义为风险比的 95%置信区间上限小于 1.3），而且优于安慰剂（定义为风险比的 95%置信区间上限分别为 1.0 和 1.3），主要复合终点为心血管死亡、心肌梗死、卒中和不稳定型心绞痛住院。
结果
6068 名接受随机分组的患者中位随访 25 个月。利西那肽组有 406 例（13.4%）患者发生主要终点事件，安慰剂组有 399 例（13.2%）（风险比，1.02；95%置信区间[CI]，0.89 至 1.17），这表明利西那肽不劣于安慰剂（P<0.001），但不优于安慰剂（P=0.81）。两组心力衰竭住院率（利西那肽组风险比为 0.96；95%CI，0.75 至 1.23）或死亡率（风险比为 0.94；95%CI，0.78 至 1.13）无显著差异。与安慰剂相比，利西那肽并未增加严重不良事件或严重低血糖、胰腺炎、胰腺肿瘤或过敏反应的发生率。
结论
在近期发生急性冠状动脉综合征的 2 型糖尿病患者中，利西那肽联合常规治疗并未显著改变主要心血管事件或其他严重不良事件的发生率。（由 Sanofi 资助；ELIXA ClinicalTrials.gov 编号，NCT01147250。）
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