Ambrosy Andrew P, Sauer Andrew J, Patel Shachi, Windsor Sheryl L, Borlaug Barry A, Husain Mansoor, Inzucchi Silvio E, Kitzman Dalane W, McGuire Darren K, Shah Sanjiv J, Sharma Kavita, Umpierrez Guillermo, Kosiborod Mikhail N
Department of Cardiology, Kaiser Permanente, San Francisco, California, USA.
Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
ESC Heart Fail. 2025 Jun;12(3):1676-1681. doi: 10.1002/ehf2.15184. Epub 2024 Dec 24.
Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR).
We conducted a pooled participant-level analysis of two double-blind, randomized trials, DEFINE-HF (n = 236) and PRESERVED-HF (n = 324), which evaluated dapagliflozin versus placebo. Both multicentre studies enrolled adults with HF, New York Heart Association Class II or higher, elevated natriuretic peptides, and an EF < 40% in DEFINE-HF or >45% in PRESERVED-HF. The primary exposure was eGFR. The main outcome was the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at 12 weeks. Across both trials, there were 583 (99.3%) participants with a baseline eGFR. The median (25th, 75th) eGFR was 59 (46, 77) mL/min/1.73 m. Dapagliflozin improved KCCQ-CSS at 12 weeks [placebo-adjusted difference, +5.0 points, 95% confidence interval (CI) 2.6-7.5; P < 0.001], and this was consistent in participants with an eGFR ≥ 60 (+6.0 points, 95% CI 2.4-9.7; P = 0.001) and eGFR < 60 (+4.1 points, 95% CI 0.5-7.7; P = 0.025) (P interaction = 0.46). The benefits of dapagliflozin on KCCQ-CSS remained robust across eGFR when modelled as a continuous variable (P interaction = 0.48).
Dapagliflozin led to early and clinically meaningful improvements in health status in HF patients, regardless of EF or baseline eGFR.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可改善射血分数（EF）范围内心力衰竭（HF）患者的健康状况和预后。基线肾病在HF患者中很常见，使HF管理复杂化，且与较差的健康状况密切相关。本研究旨在评估达格列净对健康状况的治疗效果是否因估计肾小球滤过率（eGFR）而异。
我们对两项双盲、随机试验DEFINE-HF（n = 236）和PRESERVED-HF（n = 324）进行了汇总参与者水平分析，这两项试验评估了达格列净与安慰剂的疗效。两项多中心研究均纳入了HF患者，纽约心脏协会心功能分级为II级或更高，利钠肽升高，DEFINE-HF试验中EF < 40%，PRESERVED-HF试验中EF > 45%。主要暴露因素为eGFR。主要结局为12周时的堪萨斯城心肌病问卷临床总结评分（KCCQ-CSS）。在两项试验中，共有583名（99.3%）参与者有基线eGFR。eGFR的中位数（第25百分位数，第75百分位数）为59（46，77）mL/min/1.73m²。达格列净在12周时改善了KCCQ-CSS[安慰剂校正差异为+5.0分，95%置信区间（CI）2.6 - 7.5；P < 0.001]，在eGFR≥60的参与者中（+6.0分，95%CI 2.4 - 9.7；P = 0.001）和eGFR < 60的参与者中（+4.1分，95%CI 0.5 - 7.7；P = 0.025）也是如此（P交互作用 = 0.46）。当将eGFR作为连续变量进行建模时，达格列净对KCCQ-CSS的益处仍然显著（P交互作用 = 0.48）。
无论EF或基线eGFR如何，达格列净均可使HF患者的健康状况在早期得到具有临床意义的改善。
