美国布列根和妇女医院Scott D. Solomon团队研究了达格列净治疗射血分数轻度降低或保留的心力衰竭患者的疗效。这一研究成果发表在2022年8月27日出版的《新英格兰医学杂志》上。

钠-葡萄糖共转运蛋白2（SGLT2）抑制剂可降低慢性心力衰竭和左心室射血分数为40%或更低的患者因心力衰竭住院和心血管死亡的风险。SGLT2抑制剂是否对左室射血分数较高的患者仍有效尚不确定。

研究组随机分配6263名左室射血分数超过40%的心力衰竭患者，除常规治疗外，分别接受达格列净（剂量为10mg，每日一次）或安慰剂治疗。主要结局是心力衰竭恶化（定义为因心力衰竭而非计划住院或因心力衰竭而紧急就诊）或心血管死亡，如时间-事件分析所评估。

中位随访2.3年，达格列净组3131名患者中有512名（16.4%）出现主要结局，安慰剂组3132名患者中有610名（19.5%），危险比为0.82，组间差异显著。达格列净组中有368名患者（11.8%）出现心力衰竭恶化，安慰剂组中有455名（14.5%），危险比为0.79；达格列净组中有231名患者（7.4%）心血管死亡，安慰剂组中有261名（8.3%），危险比为0.88。

达格列净组的总事件和症状负担低于安慰剂组。上述结果在左心室射血分数为60%或以上的患者和左心室射血分数低于60%的患者中相似，在预先指定的亚组中结果相似，包括患或不患有糖尿病的患者。两组不良事件的发生率相似。

研究结果表明，达格列净降低了射血分数轻度降低或保留的心力衰竭患者心力衰竭恶化或心血管死亡的综合风险。

附：英文原文

Title: Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction

Author: Scott D. Solomon, M.D.,, John J.V. McMurray, M.D.,, Brian Claggett, Ph.D.,, Rudolf A. de Boer, M.D.,, David DeMets, Ph.D.,, Adrian F. Hernandez, M.D.,, Silvio E. Inzucchi, M.D.,, Mikhail N. Kosiborod, M.D.,, Carolyn S.P. Lam, M.D.,, Felipe Martinez, M.D.,, Sanjiv J. Shah, M.D.,, Akshay S. Desai, M.D.,, Pardeep S. Jhund, M.B., Ch.B., Ph.D.,, Jan Belohlavek, M.D.,, Chern-En Chiang, M.D.,, C. Jan Willem Borleffs, M.D.,, Josep Comin-Colet, M.D., Ph.D.,, Dan Dobreanu, M.D.,, Jaroslaw Drozdz, M.D., Ph.D.,, James C. Fang, M.D.,, Marco Antonio Alcocer-Gamba, M.D.,, Waleed Al Habeeb, M.D.,, Yaling Han, M.D.,, Jose Walter Cabrera Honorio, M.D.,, Stefan P. Janssens, M.D.,, Tzvetana Katova, M.D.,, Masafumi Kitakaze, M.D.,, Béla Merkely, M.D., Ph.D.,, Eileen O’Meara, M.D.,, Jose Francisco Kerr Saraiva, M.D., Ph.D.,, Sergey N. Tereshchenko, M.D.,, Jorge Thierer, M.D.,, Muthiah Vaduganathan, M.D., M.P.H.,, Orly Vardeny, Pharm.D.,, Subodh Verma, M.D.,, Vinh Nguyen Pham, M.D.,, Ulrica Wilderng, Ph.D.,, Natalia Zaozerska, M.D., Ph.D.,, Erasmus Bachus, M.D., Ph.D.,, Daniel Lindholm, M.D., Ph.D.,, Magnus Petersson, M.D., Ph.D.,, and Anna Maria Langkilde, M.D., Ph.D.

Issue&Volume: 2022-08-27

Abstract:

Background

Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain.

Methods

We randomly assigned 6263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis.

Results

Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients (16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.92; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79; 95% CI, 0.69 to 0.91); cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively (hazard ratio, 0.88; 95% CI, 0.74 to 1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups.

Conclusions

Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction.

DOI: 10.1056/NEJMoa2206286

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2206286