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替格瑞洛治疗稳定型冠心病合并糖尿病患者
Ticagrelor in Patients with Stable Coronary Disease and Diabetes


P. Gabriel Steg ... 心脑血管疾病 糖尿病 • 2019.10.03
相关阅读
• 在后他汀时代是否应将阿司匹林用于一级预防 • 替格瑞洛可否成为新型抗感染药物

对THEMIS“女神”的深度理解

 

朱云鹏†,秦国友‡,赵强†*

†上海交通大学医学院附属瑞金医院心脏外科;‡复旦大学公共卫生学院生物统计学教研室

*通讯作者

 

如何正确地报告和解读前瞻性随机对照研究,这不仅是(以医生为主体的)读者的事,也是杂志编辑的份内事,更需要方法学家和统计学家的参与1。事实上,曾有国外的执业医师认为,尽管有医学继续教育课程,他们依然没有能力批判性地阅读医学文献2

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摘要


背景

无心肌梗死或卒中病史的稳定型冠心病合并糖尿病患者发生心血管事件的风险高。在阿司匹林的基础上加用替格瑞洛可否改善这一人群的结局尚未明确。

 

方法

在这项随机双盲试验中,我们将稳定型冠心病合并2型糖尿病的≥50岁患者随机分组,分别接受替格瑞洛联合阿司匹林治疗和安慰剂联合阿司匹林治疗。有心肌梗死或卒中病史的患者被排除。主要疗效结局是由心血管原因死亡、心肌梗死或卒中构成的复合结局。主要安全性结局是根据心肌梗死溶栓(Thrombolysis in Myocardial Infarction,TIMI)标准定义的大出血。

 

结果

共有19,220例患者接受了随机分组。中位随访期为39.9个月。替格瑞洛组的永久性停药发生率高于安慰剂组(34.5% vs. 25.4%)。替格瑞洛组的缺血性心血管事件(主要疗效结局)发生率低于安慰剂组(7.7%vs. 8.5%;风险比,0.90;95% CI,0.81~0.99;P=0.04),而TIMI大出血(2.2% vs. 1.0%;风险比,2.32;95% CI,1.82~2.94;P<0.001)和颅内出血(0.7% vs. 0.5%;风险比,1.71;95% CI,1.18~2.48;P=0.005)发生率高于安慰剂组。致死性出血的发生率无显著差异(0.2% vs. 0.1%;风险比,1.90;95% CI,0.87~4.15;P=0.11)。在替格瑞洛组和安慰剂组中,探索性复合结局不可逆损害(全因死亡、心肌梗死、卒中、致死性出血或颅内出血)的发生率相似(10.1% vs. 10.8%;风险比,0.93;95% CI,0.86~1.02)。

 

结论

在无心肌梗死和卒中病史的稳定型冠心病合并糖尿病患者中,与安慰剂联合阿司匹林治疗相比,接受替格瑞洛联合阿司匹林治疗患者的缺血性心血管事件发生率较低,但大出血发生率较高(由阿斯利康资助;THEMIS在ClinicalTrials.gov注册号为NCT01991795)。





作者信息

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*
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.). Address reprint requests to Dr. Steg at the Department of Cardiology, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris, France, or at gabriel.steg@aphp.fr; or to Dr. Bhatt at Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis St., Boston, MA 02115, or at dlbhattmd@post.harvard.edu. *A list of THEMIS investigators and committee members is provided in the Supplementary Appendix, available at NEJM.org.

 

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