英国格拉斯哥大学John J. V. McMurray团队探讨了达格列净对有无糖尿病的心力衰竭患者心衰恶化和心血管死亡的影响。该研究于2020年3月27日发表在《美国医学会杂志》上。

对于射血分数降低的心力衰竭（HFrEF），需要额外治疗。钠-葡萄糖共转运蛋白2（SGLT2）抑制剂可能是HFrEF患者的有效治疗方法，即使没患糖尿病。

为了评估达格列净对合并和不合并糖尿病的HFrEF患者的疗效，研究组在20个国家/地区的410个站点进行了一项3期随机试验。2017年2月15日至2018年8月17日，研究组招募了4744例纽约心脏协会II-IV级的患者，其射血分数低于40%且血浆N末端B型钠尿肽前体升高。所有患者在常规治疗基础上，每天补充一次达格列净或安慰剂。主要结果为心衰恶化或心血管死亡。

4744例患者的平均年龄为66岁，女性占23%，无糖尿病者占55%，共有4742例完成了试验。在无糖尿病的参与者中，达格列净组主要结果发生率为13.2%，安慰剂组为17.7%，风险比为0.73。在糖尿病参与者中，达格列净组主要结果发生率为20.0%，安慰剂组为25.5%，风险比为0.75。

在没有糖尿病且糖化血红蛋白水平低于5.7%的参与者中，达格列净组主要结果发生率为12.1%，安慰剂组为16.9%，风险比为0.67。糖化血红蛋白超过5.7%的参与者中，达格列净组主要结果发生率为13.7%，安慰剂组为18.0%，风险比为0.74。

在没有糖尿病的患者中，达格列净组中血容量减少等不良反应的发生率为7.3%，安慰剂组中为6.1%；在糖尿病患者中，达格列净组和安慰剂的不良反应发生率均为7.8%。在非糖尿病患者中，达格列净组的肾脏不良事件为4.8%，安慰剂组为6.0%；在糖尿病患者中，达格列净组为8.5%，安慰剂组为8.7%。

总之，达格列净治疗HFrEF患者，无论其是否有糖尿病，与安慰剂相比，可显著降低心衰恶化和心血管死亡的风险。

附：英文原文

Title: Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes

Author: Mark C. Petrie, Subodh Verma, Kieran F. Docherty, Silvio E. Inzucchi, Inder Anand, Jan Bělohlávek, Michael Bhm, Chern-En Chiang, Vijay K. Chopra, Rudolf A. de Boer, Akshay S. Desai, Mirta Diez, Jaroslaw Drozdz, Andre Dukát, Junbo Ge, Jonathan Howlett, Tzvetana Katova, Masafumi Kitakaze, Charlotta E. A. Ljungman, Béla Merkely, Jose C. Nicolau, Eileen OMeara, Pham Nguyen Vinh, Morten Schou, Sergey Tereshchenko, Lars Kber, Mikhail N. Kosiborod, Anna Maria Langkilde, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, Mikaela Sjstrand, Scott D. Solomon, Per Johanson, Peter J. Greasley, David Boulton, Olof Bengtsson, Pardeep S. Jhund, John J. V. McMurray

Issue&Volume: 2020-03-27

Abstract: Abstract

Importance  Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.

Objective  To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.

Design, Setting, and Participants  Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.

Interventions  Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.

Main Outcomes and Measures  The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.

Results  Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction=.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction=.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.

Conclusions and Relevance  In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.

DOI: 10.1001/jama.2020.1906

Source: https://jamanetwork.com/journals/jama/fullarticle/2763950