Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Eur J Heart Fail. 2022 Oct;24(10):1892-1901. doi: 10.1002/ejhf.2652. Epub 2022 Aug 27.
This pre-specified analysis of the DELIVER trial examined whether clinical benefits of dapagliflozin in heart failure (HF) with left ventricular ejection fraction (LVEF) >40% varied by baseline New York Heart Association (NYHA) class and examined the treatment effects on NYHA class over time.
Treatment effects of dapagliflozin by baseline NYHA class II (n = 4713) versus III/IV (n = 1549) were examined on the primary endpoint (cardiovascular death or worsening HF event) and key secondary endpoints. Effects of dapagliflozin on change in NYHA class at 4, 16, and 32 weeks were also evaluated. Higher baseline NYHA class was associated with older age, female sex, greater comorbidity burden, lower LVEF, and higher natriuretic peptide levels. Participants with baseline NYHA class III/IV, as compared with II, were independently more likely to experience the primary endpoint (adjusted hazard ratio [HR] 1.16 [95% confidence interval, 1.02-1.33]) and all-cause death (adjusted HR 1.22 [1.06-1.40]). Dapagliflozin consistently reduced the risk of the primary endpoint compared with placebo, irrespective of baseline NYHA class (HR 0.81 [0.70-0.94] for NYHA class II vs. HR 0.80 [0.65-0.98] for NYHA class III/IV; p = 0.921). Participants with NYHA class III/IV had greater improvement in Kansas City Cardiomyopathy Questionnaire total symptom scores between baseline and 32 weeks (+4.8 [2.5-7.1]) versus NYHA class II (+1.8 [0.7-2.9]; p = 0.011). Dapagliflozin was associated with higher odds of any improvement in NYHA class (odds ratio [OR] 1.32 [1.16-1.51]), as well as improvement to NYHA class I (OR 1.43 [1.17-1.75]), versus placebo at 32 weeks, with benefits seen as early as 4 weeks.
Among symptomatic patients with HF and LVEF >40%, treatment with dapagliflozin provided clinical benefit irrespective of baseline NYHA class and was associated with early and sustained improvements in NYHA class over time.
本 DELIVER 试验的预先设定分析旨在考察达格列净对射血分数（LVEF）>40%的心衰（HF）患者的临床获益是否因基线纽约心脏协会（NYHA）心功能分级而有所不同，并探讨达格列净对 NYHA 心功能分级的治疗效果随时间的变化情况。
本分析考察了达格列净在基线 NYHA 心功能分级 II 级（n=4713）与 III/IV 级（n=1549）患者中的主要终点（心血管死亡或 HF 恶化事件）和关键次要终点的治疗效果。还评估了 4、16 和 32 周时达格列净对 NYHA 心功能分级变化的影响。较高的基线 NYHA 心功能分级与年龄较大、女性、合并症负担较重、LVEF 较低和脑钠肽水平较高有关。与 NYHA 心功能分级 II 级相比，基线 NYHA 心功能分级 III/IV 级的患者更有可能发生主要终点（校正后的危险比 [HR] 1.16 [95%置信区间，1.02-1.33]）和全因死亡（校正后的 HR 1.22 [1.06-1.40]）。与安慰剂相比，达格列净始终降低主要终点的风险，与基线 NYHA 心功能分级无关（NYHA 心功能分级 II 级 vs. NYHA 心功能分级 III/IV 级的 HR 0.81 [0.70-0.94]；NYHA 心功能分级 III/IV 级 vs. HR 0.80 [0.65-0.98]；p=0.921）。与 NYHA 心功能分级 II 级相比，基线至 32 周时 NYHA 心功能分级 III/IV 级患者的堪萨斯城心肌病问卷总症状评分改善更大（+4.8 [2.5-7.1] vs. +1.8 [0.7-2.9]；p=0.011）。与安慰剂相比，达格列净与 NYHA 心功能分级任何改善的更高几率相关（优势比 [OR] 1.32 [1.16-1.51]），以及改善至 NYHA 心功能分级 I 的几率更高（OR 1.43 [1.17-1.75]），在 32 周时，这种获益从 4 周时就已经开始出现。
在射血分数>40%的有症状 HF 患者中，达格列净治疗可带来临床获益，无论基线 NYHA 心功能分级如何，且与 NYHA 心功能分级随时间的改善有关，且改善可早期持续出现。
