Importance An initial decline in estimated glomerular filtration rate (eGFR) is expected after initiating a sodium-glucose cotransporter-2 inhibitor (SGLT2i) and has been observed across patients with diabetes, chronic kidney disease, and heart failure. Objective To examine the implications of initial changes in eGFR among patients with heart failure with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. Design, Setting, and Participants This was a prespecified analysis of the results of the DELIVER randomized clinical trial, which was an international multicenter study of patients with EF greater than 40% and eGFR greater than or equal to 25. The DELIVER trial took place from August 2018 to March 2022. Data for the current prespecified study were analyzed from February to October 2023. Intervention Dapagliflozin, 10 mg per day, or placebo. Main Outcomes and Measures In this prespecified analysis, the frequency of an initial eGFR decline (baseline to month 1) was compared between dapagliflozin and placebo. Cox models adjusted for baseline eGFR and established prognostic factors were fit to estimate the association of an initial eGFR decline with cardiovascular (cardiovascular death or heart failure event) and kidney (≥50% eGFR decline, eGFR<15 or dialysis, death from kidney causes) outcomes, landmarked at month 1, stratified by diabetes. Results Study data from 5788 participants (mean [SD] age, 72 [10] years; 3253 male [56%]) were analyzed. The median (IQR) change in eGFR level from baseline to month 1 was -1 (-6 to 5) with placebo and -4 (-9 to 1) with dapagliflozin (difference, -3; P < .001). A higher proportion of patients assigned to dapagliflozin developed an initial eGFR decline greater than 10% vs placebo (1144 of 2892 [40%] vs 737 of 2896 [25%]; odds ratio, 1.9; 95% CI, 1.7-2.1; P difference <.001). An initial eGFR decline of greater than 10% (vs ≤10%) was associated with a higher risk of the primary cardiovascular outcome among those randomized to placebo (adjusted hazard ratio [aHR], 1.33; 95% CI, 1.10-1.62) but not among those randomized to dapagliflozin (aHR, 0.90; 95% CI, 0.74-1.09; P for interaction = .01). Similar associations were observed when alternative thresholds of initial eGFR decline were considered and when analyzed as a continuous measure. An initial eGFR decline of greater than 10% was not associated with adverse subsequent kidney composite outcomes in dapagliflozin-treated patients (aHR, 0.94; 95% CI, 0.49-1.82). Conclusions and Relevance Among patients with HFmrEF or HFpEF treated with dapagliflozin, an initial eGFR decline was frequent but not associated with subsequent risk of cardiovascular or kidney events. These data reinforce clinical guidance that SGLT2is should not be interrupted or discontinued in response to an initial eGFR decline. Trial Registration ClinicalTrials.gov Identifier: NCT03619213.

中文翻译：

---

射血分数轻度降低或保留的心力衰竭患者使用达格列净后估计肾小球滤过率下降：DELIVER 随机临床试验的预先指定二次分析。

重要性 在开始使用钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT2i) 后，估计肾小球滤过率 (eGFR) 预计会出现初步下降，并且已在糖尿病、慢性肾病和心力衰竭患者中观察到这一情况。目的 探讨参加达格列净改善射血分数保留心力衰竭患者生活评价 (DELIVER) 的射血分数轻度降低 (HFmrEF) 或射血分数保留 (HFpEF) 心力衰竭患者 eGFR 初始变化的意义审判。设计、设置和参与者 这是对 DELIVER 随机临床试验结果的预先指定分析，该试验是一项针对 EF 大于 40% 且 eGFR 大于或等于 25 的患者进行的国际多中心研究。DELIVER 试验于2018 年 8 月至 2022 年 3 月。当前预定研究的数据于 2023 年 2 月至 10 月进行分析。干预措施：达格列净，每天 10 毫克，或安慰剂。主要结果和措施 在这项预先指定的分析中，比较了达格列净和安慰剂的初始 eGFR 下降频率（基线至第 1 个月）。根据基线 eGFR 和既定预后因素调整的 Cox 模型适合估计初始 eGFR 下降与心血管（心血管死亡或心力衰竭事件）和肾脏（eGFR 下降≥50%、eGFR<15 或透析、肾脏原因死亡）的关联）结果，以第 1 个月为标志，按糖尿病分层。结果 对 5788 名参与者（平均 [SD] 年龄，72 [10] 岁；3253 名男性 [56%]）的研究数据进行了分析。eGFR 水平从基线到第 1 个月的中位 (IQR) 变化，安慰剂组为 -1（-6 至 5），达格列净组为 -4（-9 至 1）（差异为 -3；P < .001）。与安慰剂组相比，接受达格列净治疗的患者中，初始 eGFR 下降超过 10% 的患者比例较高（2892 名患者中有 1144 名患者[40%] vs 2896 名患者中有 737 名患者[25%]；比值比，1.9；95% CI，1.7-2.1；P差异<.001）。在随机接受安慰剂的患者中，初始 eGFR 下降超过 10%（对比 ≤10%）与主要心血管结局风险较高相关（调整后风险比 [aHR]，1.33；95% CI，1.10-1.62），但不在随机接受达格列净组的患者中（aHR，0.90；95% CI，0.74-1.09；交互作用 P = 0.01）。当考虑初始 eGFR 下降的替代阈值并作为连续测量进行分析时，观察到类似的关联。在达格列净治疗的患者中，初始 eGFR 下降超过 10% 与随后的不良肾脏复合结局无关（aHR，0.94；95% CI，0.49-1.82）。结论和相关性 在接受达格列净治疗的 HFmrEF 或 HFpEF 患者中，初始 eGFR 经常下降，但与随后的心血管或肾脏事件风险无关。这些数据强化了临床指导，即不应因最初的 eGFR 下降而中断或终止 SGLT2is。试验注册 ClinicalTrials.gov 标识符：NCT03619213。