BHF Cardiovascular Research Centre, University of Glasgow, UK (C.A., K.F.D., M.C.P., P.S.J., J.J.V.M.).
Department of Clinical Pharmacy and Pharmacology (H.J.L.H.), University Medical Center Groningen, University of Groningen, The Netherlands.
Circulation. 2022 Aug 9;146(6):438-449. doi: 10.1161/CIRCULATIONAHA.121.058910. Epub 2022 Apr 20.
In a post hoc analysis, the frequency of occurrence of an early decline (dip) in estimated glomerular filtration rate (eGFR) after initiation of dapagliflozin and its association with outcomes were evaluated in patients with heart failure and reduced ejection fraction randomized in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial.
Patients with heart failure with reduced ejection fraction with or without type 2 diabetes and an eGFR ≥30 mL·min·1.73 m were randomized to placebo or dapagliflozin 10 mg daily. The primary outcome was the composite of worsening heart failure or cardiovascular death. The extent of the dip in eGFR between baseline and 2 weeks, patient characteristics associated with a >10% decline, and cardiovascular outcomes and eGFR slopes in participants experiencing this decline were investigated. Time-to-event outcomes were assessed in Cox regression from 14 days; eGFR slopes were assessed with repeated-measures mixed-effect models.
The mean change in eGFR between day 0 and 14 was -1.1 mL·min·1.73 m (95% CI, -1.5 to -0.7) with placebo and -4.2 mL·min·1.73 m (95% CI, -4.6 to -3.9) with dapagliflozin, giving a between-treatment difference of 3.1 mL·min·1.73 m (95% CI, 2.6-3.7). The proportions of patients randomized to dapagliflozin experiencing a >10%, >20%, and >30% decline in eGFR were 38.2%, 12.6%, and 3.4%, respectively; for placebo, they were 21.0%, 6.4%, and 1.3%, respectively. The odds ratio for a >10% early decline in eGFR with dapagliflozin compared with placebo was 2.36 (95% CI, 2.07-2.69; <0.001). Baseline characteristics associated with a >10% decline in eGFR on dapagliflozin were older age, lower eGFR, higher ejection fraction, and type 2 diabetes. The hazard ratio for the primary outcome in patients in the placebo group experiencing a >10% decline in eGFR compared with ≤10% decline in eGFR was 1.45 (95% CI, 1.19-1.78). The corresponding hazard ratio in the dapagliflozin group was 0.73 (95% CI, 0.59-0.91; <0.001). A >10% initial decline in eGFR was not associated with greater long-term decline in eGFR or more adverse events.
The average dip in eGFR after dapagliflozin was started was small and associated with better clinical outcomes compared with a similar decline on placebo in patients with heart failure with reduced ejection fraction. Large declines in eGFR were uncommon with dapagliflozin.
URL: https://www.
gov; Unique identifier: NCT03036124.
在一项事后分析中，评估了心力衰竭和射血分数降低患者在开始使用达格列净后肾小球滤过率（eGFR）早期下降（下降）的发生率及其与结局的关系，这些患者随机分配至达格列净和预防心力衰竭不良结局试验。
患有射血分数降低的心力衰竭且伴有或不伴有 2 型糖尿病和 eGFR≥30mL·min·1.73m的患者随机分配至安慰剂或达格列净 10mg 每日一次。主要结局为心力衰竭恶化或心血管死亡的复合结局。评估了基线至 2 周之间 eGFR 下降的程度、与 eGFR 下降超过 10%相关的患者特征，以及经历这种下降的参与者的心血管结局和 eGFR 斜率。使用 Cox 回归从第 14 天评估时间-事件结局；使用重复测量混合效应模型评估 eGFR 斜率。
与安慰剂相比，达格列净治疗组从第 0 天到第 14 天的 eGFR 平均变化为-1.1mL·min·1.73m（95%CI，-1.5 至-0.7），达格列净组为-4.2mL·min·1.73m（95%CI，-4.6 至-3.9），治疗组间差异为 3.1mL·min·1.73m（95%CI，2.6-3.7）。接受达格列净治疗的患者中，随机接受安慰剂的患者分别有 38.2%、12.6%和 3.4%发生 eGFR 下降超过 10%、20%和 30%，而接受安慰剂的患者分别有 21.0%、6.4%和 1.3%发生 eGFR 下降超过 10%、20%和 30%。与安慰剂相比，达格列净治疗的 eGFR 早期下降超过 10%的患者发生 eGFR 早期下降的优势比为 2.36（95%CI，2.07-2.69；<0.001）。与达格列净治疗的 eGFR 下降超过 10%相关的基线特征为年龄较大、eGFR 较低、射血分数较高和 2 型糖尿病。与 eGFR 下降≤10%的安慰剂组患者相比，eGFR 下降超过 10%的安慰剂组患者的主要结局的风险比为 1.45（95%CI，1.19-1.78）。达格列净组的相应风险比为 0.73（95%CI，0.59-0.91；<0.001）。eGFR 初始下降超过 10%与长期 eGFR 下降或更多不良事件无关。
与安慰剂相比，射血分数降低的心力衰竭患者开始使用达格列净后 eGFR 的平均下降幅度较小，与安慰剂相似的下降相比，临床结局更好。达格列净治疗很少出现 eGFR 大幅下降。
gov；独特标识符：NCT03036124。
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