替格瑞洛在稳定型冠心病合并糖尿病患者中的应用。
Ticagrelor in Patients with Stable Coronary Disease and Diabetes.
机构信息
From the French Alliance for Cardiovascular Trials, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Université de Paris, INSERM Unité 1148 (P.G.S.), Assistance Publique-Hôpitaux de Paris (P.G.S., T.S.), Hôpital Saint Antoine, Department of Clinical Pharmacology, Unité de Recherche Clinique (T.S.), and Sorbonne Université (T.S.) - all in Paris; the National Heart and Lung Institute, Imperial College and Royal Brompton Hospital, London (P.G.S., K.F.); Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School (D.L.B.) and Baim Institute for Clinical Research (Y.L.) - both in Boston; the Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON (S.R.M.), and Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.) - both in Canada; Stanford University, Stanford, CA (R.A.H.); the Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala (C.H.), and AstraZeneca BioPharmaceuticals Research and Development, Mölndal (M.A., A.H., W.R., M.L.-Z.) - both in Sweden; the Department of Cardiology, Medical University of Warsaw, Warsaw, Poland (G.O.); City Clinical Hospital No. 51, State Health Care Agency, Moscow (D.Z.); Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China (J.G.); Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (J.C.N.); Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile (R.C.); Northwest Clinics, Department of Cardiology, Alkmaar, Dutch Network for Cardiovascular Research, Utrecht, and Department of Cardiology, Radboud University Medical Center, Nijmegen - all in the Netherlands (J.H.C.); and Cardiocenter Charles University, Third Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic (P.W.).
出版信息
N Engl J Med. 2019 Oct 3;381(14):1309-1320. doi: 10.1056/NEJMoa1908077. Epub 2019 Sep 1.
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.).
背景
患有稳定型冠状动脉疾病和糖尿病但未发生心肌梗死或中风的患者存在发生心血管事件的高风险。在该人群中，加用替格瑞洛是否能改善阿司匹林的治疗效果尚不清楚。
方法
在这项随机、双盲试验中，我们将年龄在 50 岁及以上且患有稳定型冠状动脉疾病和 2 型糖尿病的患者随机分为替格瑞洛加阿司匹林组或安慰剂加阿司匹林组。排除有心肌梗死或中风病史的患者。主要疗效终点是心血管死亡、心肌梗死或中风的复合终点。主要安全性终点是根据血栓形成溶栓试验（TIMI）标准定义的大出血。
结果
共 19220 例患者接受了随机分组。中位随访时间为 39.9 个月。替格瑞洛组的永久性停药率高于安慰剂组（34.5% vs. 25.4%）。替格瑞洛组的缺血性心血管事件发生率（主要疗效终点）低于安慰剂组（7.7% vs. 8.5%；风险比，0.90；95%置信区间 [CI]，0.81 至 0.99；P=0.04），而 TIMI 大出血发生率较高（2.2% vs. 1.0%；风险比，2.32；95% CI，1.82 至 2.94；P<0.001），颅内出血发生率也较高（0.7% vs. 0.5%；风险比，1.71；95% CI，1.18 至 2.48；P=0.005）。致命性出血发生率无显著差异（0.2% vs. 0.1%；风险比，1.90；95% CI，0.87 至 4.15；P=0.11）。替格瑞洛组和安慰剂组不可逆性损害（任何原因所致死亡、心肌梗死、中风、致命性出血或颅内出血）的发生率相似（10.1% vs. 10.8%；风险比，0.93；95% CI，0.86 至 1.02）。
结论
在无心肌梗死或中风病史的稳定型冠状动脉疾病和糖尿病患者中，与安慰剂加阿司匹林组相比，替格瑞洛加阿司匹林组的缺血性心血管事件发生率较低，但大出血发生率较高。（由阿斯利康公司资助；THEMIS 临床试验.gov 编号，NCT01991795。）
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