法国巴黎比沙医院P. Gabriel Steg研究组和美国哈佛医学院Deepak L. Bhatt研究组合作，分析了替卡格雷治疗稳定型冠心病和糖尿病患者的疗效。2019年9月1日，知名医学期刊《新英格兰医学杂志》在线发表了这一成果。

在这项随机、双盲试验中，研究人员将19220名50岁及以上、无心肌梗塞或中风史的稳定冠状动脉疾病和2型糖尿病患者随机分为替卡格雷联合阿司匹林组和安慰剂联合阿司匹林组。缺血性心血管事件包括心血管死亡、心肌梗死或中风。

中位随访39.9个月后，与安慰剂组相比，替卡格雷组的永久性停药频率更高（34.5% vs 25.4%）。替卡格雷组缺血性心血管事件的发生率为7.7%，低于安慰剂组（8.5%），风险比为0.90；但心肌梗死溶栓（TIMI）大出血和颅内出血的发生率分别为2.2%和0.7%，均显著高于安慰剂组（1.0%和0.5%），风险比分别为2.32和1.71。两组间致命性出血的发生率没有显著差异，总体不可逆损害（全因死亡、心肌梗死、中风、致命性出血或颅内出血）的发生率也相差无几。

在无心肌梗死或中风史的稳定冠状动脉疾病和糖尿病患者中，与安慰剂加阿司匹林相比，接受替卡格雷联合阿司匹林治疗的患者缺血性心血管事件发生率较低，但大出血发生率较高。

据了解，没有心肌梗塞或中风史的稳定冠脉疾病和糖尿病患者发生心血管事件的风险很高。阿司匹林联合替卡格雷能否改善这一人群的预后尚不清楚。

附：英文原文

Title: Ticagrelor in Patients with Stable Coronary Disease and Diabetes

Author: P. Gabriel Steg, M.D., Deepak L. Bhatt, M.D., M.P.H., Tabassome Simon, M.D., Kim Fox, M.D., Shamir R. Mehta, M.D., Robert A. Harrington, M.D., Claes Held, M.D., Marielle Andersson, M.Sc., Anders Himmelmann, M.D., Wilhelm Ridderstråle, M.D., Maria Leonsson-Zachrisson, M.D., Yuyin Liu, M.S., Grzegorz Opolski, M.D., Dmitry Zateyshchikov, M.D., Junbo Ge, M.D., José C. Nicolau, M.D., Ramón Corbalán, M.D., Jan H. Cornel, M.D., Petr Widimský, M.D., and Lawrence A. Leiter, M.D. for the THEMIS Steering Committee and Investigators*

Issue&Volume: September 1, 2019

Abstract：

BACKGROUND
Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear.

METHODS
In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria.

RESULTS
A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P=0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P=0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P=0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02).

CONCLUSIONS
In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.)