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sotagliflozin治疗近期心力衰竭恶化的糖尿病患者
Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure


Deepak L. Bhatt ... 心脑血管疾病 糖尿病 • 2021.01.14
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• 1型糖尿病患者胰岛素治疗中加用sotagliflozin的效果

摘要


背景

钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂降低了稳定型心力衰竭患者因心力衰竭住院或因心血管原因死亡的风险。然而,在患者发生失代偿性心力衰竭后不久开始使用SGLT2抑制剂的安全性和疗效尚未明确。

 

方法

我们开展了一项多中心、双盲试验,本试验将近期因心力衰竭恶化住院的2型糖尿病患者随机分配接受sotagliflozin或安慰剂治疗。主要终点是因心血管原因死亡以及因心力衰竭住院和紧急就诊(首次和后续事件)的总数。本试验因失去申办方资助而提前结束。

 

结果

共计1,222例患者接受了随机分组(sotagliflozin组608例,安慰剂组614例),并接受了中位9.0个月随访;48.8%的患者在出院前,51.2%的患者在出院后2日(中位数)接受了首剂sotagliflozin或安慰剂给药。这些患者发生了600起主要终点事件(sotagliflozin组245起,安慰剂组355起)。sotagliflozin组的主要终点事件发生率(每100患者-年的事件数量)低于安慰剂组(51.0 vs. 76.3;风险比,0.67;95%置信区间[CI],0.52~0.85;P<0.001)。sotagliflozin组和安慰剂组的心血管原因死亡率分别为10.6例/100患者-年和12.5例/100患者-年(风险比,0.84;95% CI,0.58~1.22);sotagliflozin组和安慰剂组的全因死亡率分别为13.5例/100患者-年和16.3例/100患者-年(风险比,0.82;95% CI,0.59~1.14)。sotagliflozin组的腹泻(6.1% vs. 3.4%)和重度低血糖(1.5% vs. 0.3%)发生率高于安慰剂组。sotagliflozin组和安慰剂组发生低血压(分别为6.0%和4.6%)和急性肾损伤(分别为4.1%和4.4%)的患者百分比相似。在根据首剂给药时间分层的预设亚组中,sotagliflozin的益处一致。

 

结论

在近期心力衰竭恶化的糖尿病患者中,患者出院前或出院后不久开始的sotagliflozin治疗与安慰剂相比显著减少了因心血管原因死亡以及因心力衰竭住院和紧急就诊的总数(由赛诺菲和Lexicon Pharmaceuticals资助,SOLOIST-WHF在ClinicalTrials.gov注册号为NCT03521934)。





作者信息

Deepak L. Bhatt, M.D., M.P.H., Michael Szarek, Ph.D., P. Gabriel Steg, M.D., Christopher P. Cannon, M.D., Lawrence A. Leiter, M.D., Darren K. McGuire, M.D., M.H.Sc., Julia B. Lewis, M.D., Matthew C. Riddle, M.D., Adriaan A. Voors, M.D., Ph.D., Marco Metra, M.D., Lars H. Lund, M.D., Ph.D., Michel Komajda, M.D., Jeffrey M. Testani, M.D., M.T.R., Christopher S. Wilcox, M.D., Piotr Ponikowski, M.D., Renato D. Lopes, M.D., Ph.D., Subodh Verma, M.D., Ph.D., Pablo Lapuerta, M.D., and Bertram Pitt, M.D. for the SOLOIST-WHF Trial Investigators*
From Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B., C.P.C.); Colorado Prevention Center Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.S.); State University of New York Downstate School of Public Health, Brooklyn (M.S.); Université de Paris, French Alliance for Cardiovascular Trials, Assistance Publique–Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148 (P.G.S.), and Paris Sorbonne University and Groupe Hospitalier Paris Saint Joseph (M.K.), Paris; Li Ka Shing Knowledge Institute (L.A.L., S.V.) and the Divisions of Endocrinology and Metabolism (L.A.L.) and Cardiac Surgery (S.V.), St. Michael’s Hospital, and the Departments of Medicine and Nutritional Sciences (L.A.L) and Surgery and Pharmacology and Toxicology (S.V.), University of Toronto, Toronto; University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas (D.K.M.), and Lexicon Pharmaceuticals, The Woodlands (P.L.) — both in Texas; Vanderbilt University, Nashville (J.B.L.); the Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland (M.C.R.); University of Groningen–University Medical Center Groningen, Groningen, the Netherlands (A.A.V); Azienda Socio Sanitaria Territoriale Spedali Civili and University of Brescia, Brescia, Italy (M.M.); Karolinska Institutet, Stockholm (L.H.L.); Yale University, New Haven, CT (J.M.T.); Georgetown University, Washington, DC (C.S.W.); Wroclaw Medical University, Wroclaw, Poland (P.P.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L.); and the University of Michigan, Ann Arbor (B.P.). Address reprint requests 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 complete list of the SOLOIST-WHF trial investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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