Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes
Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes
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DOI：
10.1001/jama.2020.1906
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发表时间：
2020-04-14
影响因子：
120.7
通讯作者：
McMurray, John J. V.
中科院分区：
文献类型：
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作者：
Petrie, Mark C.;Verma, Subodh;McMurray, John J. V.
射血分数降低的心力衰竭（HFrEF）需要额外的治疗。钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂可能是HFrEF患者的有效治疗方法，即使是那些没有糖尿病的患者。目的评价达格列净治疗合并糖尿病和不合并糖尿病的心力衰竭（HFrEF）的疗效。设计、设置和参与者对在20个国家的410个研究中心进行的III期随机试验进行的探索性分析。2017年2月15日至2018年8月17日期间入组了射血分数≤ 40%且血浆N末端B型利钠肽原升高的纽约心脏协会II至IV级患者，最终随访时间为2019年6月6日。在推荐治疗基础上增加每日一次10 mg达格列净或安慰剂。主要结局和测量主要结局是心力衰竭恶化或心血管死亡的复合事件。根据基线糖尿病状态和无糖尿病患者的糖化血红蛋白水平（小于5.7% vs大于或等于5.7%）分析该结局。结果在4744例随机化患者中（平均年龄66岁; 1109例[23%]女性; 2605例[55%]无糖尿病），4742例完成了试验。在无糖尿病的受试者中，达格列净组171/1298（13.2%）和安慰剂组231/1307（17.7%）发生主要结局（风险比，0.73 [95%CI，0.60-0.88]）。在糖尿病患者中，达格列净组1075例患者中有215例（20.0%）发生主要结局，安慰剂组1064例患者中有271例（25.5%）发生主要结局（风险比，0.75 [95%CI，0.63-0.90]）（相互作用P值= 0.80）。在无糖尿病且糖化血红蛋白水平低于5.7%的患者中，达格列净组438例患者中有53例（12.1%）发生主要结局，安慰剂组419例患者中有71例（16.9%）发生主要结局（风险比，0.67 [95%CI，0.47-0.96]）。在糖化血红蛋白至少为5.7%的患者中，达格列净组860例患者中的118例（13.7%）和安慰剂组888例患者中的160例（18.0%）发生了主要结局（风险比，0.74 [95%CI，0.59-0.94]）（相互作用的P值= 0.72）。在无糖尿病患者中，达格列净组7.3%的患者和安慰剂组6.1%的患者以及糖尿病患者中，达格列净组7.8%的患者和安慰剂组7.8%的患者报告了血容量不足为不良事件。在无糖尿病患者中，达格列净组4.8%的患者和安慰剂组6.0%的患者报告了肾脏不良事件，在糖尿病患者中，达格列净组8.5%的患者和安慰剂组8.7%的患者报告了肾脏不良事件。结论和相关性在HFrEF患者随机试验的探索性分析中，与安慰剂相比，当添加到推荐治疗中时，达格列净显著降低心力衰竭恶化或心血管死亡的风险，与糖尿病状态无关。
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.