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达格列净治疗射血分数降低的心力衰竭患者
Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction


John J.V. McMurray ... 心脑血管疾病 糖尿病 • 2019.11.21
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达格列净治疗心力衰竭患者
相关阅读
• 《NEJM 期刊荟萃:心脏病学》2019年头条文章 • 应用SGLT2抑制剂减小心力衰竭的影响 • 通过抑制血管紧张素-脑啡肽酶治疗急性失代偿性心力衰竭

摘要


背景

在2型糖尿病患者中,钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂可降低因心力衰竭首次住院的风险,其机制可能与葡萄糖无关。我们需要更多关于SGLT2在射血分数降低的心力衰竭(不论是否患2型糖尿病)患者中所产生效应的数据。

 

方法

在这项3期、安慰剂对照试验中,我们将4,744例射血分数≤40%的纽约心脏学会(New York Heart Association)心功能分级Ⅱ、Ⅲ或Ⅳ级心力衰竭患者随机分组,分别接受推荐治疗+达格列净(剂量为每日1次,每次10 mg)或推荐治疗+安慰剂。主要结局是由心力衰竭恶化(因心力衰竭住院或者因心力衰竭紧急就诊并接受静脉给药治疗)或心血管原因死亡构成的复合结局。

 

结果

在中位18.2个月期间,达格列净组2,373例患者中的386例(16.3%)和安慰剂组2,371例患者中的502例(21.2%)发生了主要结局(风险比,0.74;95% CI,0.65~0.85;P<0.001)。达格列净组237例患者(10.0%)和安慰剂组326例患者(13.7%)发生了首次心力衰竭恶化事件(风险比,0.70;95% CI,0.59~0.83)。达格列净组227例患者(9.6%)和安慰剂组273例患者(11.5%)因心血管原因死亡(风险比,0.82;95% CI,0.69~0.98);两组分别有276例患者(11.6%)和329例患者(13.9%)死亡(风险比,0.83;95% CI,0.71~0.97)。糖尿病患者的观察结果与非糖尿病患者的观察结果相似。与血容量不足、肾功能障碍和低血糖相关的不良事件发生率无组间差异。

 

结论

在射血分数降低的心力衰竭患者中,不论患者是否患糖尿病,与接受安慰剂治疗的患者相比,在接受达格列净治疗的患者中,心力衰竭恶化或心血管原因死亡的风险均较低(由阿斯利康资助;DAPA-HF在ClinicalTrials.gov注册号为NCT03036124)。





作者信息

John J.V. McMurray, M.D., Scott D. Solomon, M.D., Silvio E. Inzucchi, M.D., Lars Køber, M.D., D.M.Sc., Mikhail N. Kosiborod, M.D., Felipe A. Martinez, M.D., Piotr Ponikowski, M.D., Ph.D., Marc S. Sabatine, M.D., M.P.H., Inder S. Anand, M.D., Jan Bělohlávek, M.D., Ph.D., Michael Böhm, M.D., Ph.D., Chern-En Chiang, M.D., Ph.D., Vijay K. Chopra, M.D., Rudolf A. de Boer, M.D., Ph.D., Akshay S. Desai, M.D., M.P.H., Mirta Diez, M.D., Jaroslaw Drozdz, M.D., Ph.D., Andrej Dukát, M.D., Ph.D., Junbo Ge, M.D., Jonathan G. Howlett, M.D., Tzvetana Katova, M.D., Ph.D., Masafumi Kitakaze, M.D., Ph.D., Charlotta E.A. Ljungman, M.D., Ph.D., Béla Merkely, M.D., Ph.D., Jose C. Nicolau, M.D., Ph.D., Eileen O’Meara, M.D., Mark C. Petrie, M.B., Ch.B., Pham N. Vinh, M.D., Ph.D., Morten Schou, M.D., Ph.D., Sergey Tereshchenko, M.D., Ph.D., Subodh Verma, M.D., Ph.D., Claes Held, M.D., Ph.D., David L. DeMets, Ph.D., Kieran F. Docherty, M.B., Ch.B., Pardeep S. Jhund, M.B., Ch.B., Ph.D., Olof Bengtsson, Ph. Lic., Mikaela Sjöstrand, M.D., Ph.D., and Anna-Maria Langkilde, M.D., Ph.D. for the DAPA-HF Trial Committees and Investigators*
From the BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M., M.C.P., K.F.D., P.S.J.); the Cardiovascular Division (S.D.S., A.S.D.) and the TIMI Study Group, Brigham and Women’s Hospital and Harvard Medical School (M.S.S.) — all in Boston; Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.); Rigshospitalet Copenhagen University Hospital (L.K.) and the Department of Cardiology, Gentofte University Hospital (M. Schou), Copenhagen; the Department of Medicine, Saarland University Hospital, Homburg–Saar, Germany (M.B.); Saint Luke’s Mid America Heart Institute, University of Missouri, Kansas City (M.N.K.); National University of Cordoba, Cordoba (F.A.M.), and the Division of Cardiology, Instituto Cardiovascular de Buenos Aires, Buenos Aires (M.D.) — both in Argentina; Wroclaw Medical University, Wroclaw (P.P.), and the Department of Cardiology, Medical University of Lodz, Lodz (J.D.) — both in Poland; the Department of Cardiology, University of Minnesota, Minneapolis (I.S.A.); 2nd Department of Internal Medicine, Cardiovascular Medicine, General Teaching Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic (J.B.); the Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan (C.-E.C.); the Department of Cardiology, Medanta, Gurgaon, India (V.K.C.); the Department of Cardiology, University Medical Center and University of Groningen, Groningen, the Netherlands (R.A.B.); the 5th Department of Internal Medicine, Comenius University in Bratislava, Bratislava, Slovakia (A.D.); the Department of Cardiology, Shanghai Institute of Cardiovascular Disease and Zhongshan Hospital Fudan University, Shanghai, China (J.G.); Cumming School of Medicine and Libin Cardiovascular Institute, University of Calgary, Calgary, AB (J.G.H.), the Department of Cardiology, Montreal Heart Institute, Montreal (E.O.), and the Division of Cardiac Surgery, St. Michael’s Hospital, University of Toronto, Toronto (S.V.) — all in Canada; Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria (T.K.); the Cardiovascular Division of Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (M.K.); the Department of Molecular and Clinical Medicine and Cardiology, Sahlgrenska Academy (C.E.A.L.), and AstraZeneca (O.B., M. Sjöstrand, A.M.L.), Gothenburg, and the Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University (C.H.), Uppsala — all in Sweden; the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Instituto do Coracao, Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paolo, São Paolo (J.C.N.); the Department of Internal Medicine, Tan Tao University, Tan Duc, Vietnam (P.N.V.); the Department of Myocardial Disease and Heart Failure, National Medical Research Center of Cardiology, Moscow (S.T.); and the Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison (D.L.D.).Address reprint requests to Dr. McMurray at the British Heart Foundation Cardiovascular Research Centre, University of Glasgow, 126 University Pl., Glasgow G12 8TA, United Kingdom, or at john.mcmurray@glasgow.ac.uk. *A complete list of DAPA-HF committee members and investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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