British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.H.B., P.S.J., J.J.V.M.).
Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Denmark (J.H.B.).
Circulation. 2022 Oct 18;146(16):1210-1224. doi: 10.1161/CIRCULATIONAHA.122.061754. Epub 2022 Aug 27.
Frailty is increasing in prevalence. Because patients with frailty are often perceived to have a less favorable risk/benefit profile, they may be less likely to receive new pharmacologic treatments. We investigated the efficacy and tolerability of dapagliflozin according to frailty status in patients with heart failure with mildly reduced or preserved ejection fraction randomized in DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure).
Frailty was measured using the Rockwood cumulative deficit approach. The primary end point was time to a first worsening heart failure event or cardiovascular death.
Of the 6263 patients randomized, a frailty index (FI) was calculable in 6258. In total, 2354 (37.6%) patients had class 1 frailty (FI ≤0.210; ie, not frail), 2413 (38.6%) had class 2 frailty (FI 0.211-0.310; ie, more frail), and 1491 (23.8%) had class 3 frailty (FI ≥0.311; ie, most frail). Greater frailty was associated with a higher rate of the primary end point (per 100 person-years): FI class 1, 6.3 (95% CI 5.7-7.1); class 2, 8.3 (7.5-9.1); and class 3, 13.4 (12.1-14.7; <0.001). The effect of dapagliflozin (as a hazard ratio) on the primary end point from FI class 1 to 3 was 0.85 (95% CI, 0.68-1.06), 0.89 (0.74-1.08), and 0.74 (0.61-0.91), respectively (=0.40). Although patients with a greater degree of frailty had worse Kansas City Cardiomyopathy Questionnaire scores at baseline, their improvement with dapagliflozin was greater than it was in patients with less frailty: placebo-corrected improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score at 4 months in FI class 1 was 0.3 (95% CI, -0.9 to 1.4); in class 2, 1.5 (0.3-2.7); and in class 3, 3.4 (1.7-5.1; =0.021). Adverse reactions and treatment discontinuation, although more frequent in patients with a greater degree of frailty, were not more common with dapagliflozin than with placebo irrespective of frailty class.
In DELIVER, frailty was common and associated with worse outcomes. The benefit of dapagliflozin was consistent across the range of frailty studied. The improvement in health-related quality of life with dapagliflozin occurred early and was greater in patients with a higher level of frailty.
URL: https://www.
gov; Unique identifier: NCT03619213.
衰弱的发病率正在上升。由于衰弱患者的风险/获益情况通常被认为不太理想，因此他们接受新的药物治疗的可能性较小。我们研究了达格列净在心力衰竭伴轻度射血分数降低或保留的 DELIVER（达格列净评价改善射血分数保留心力衰竭患者的生活）随机分组患者中的疗效和耐受性与虚弱状态的关系。
采用 Rockwood 累积缺陷法评估衰弱状态。主要终点为首次心力衰竭恶化事件或心血管死亡的时间。
在 6263 例随机患者中，6258 例可计算衰弱指数（FI）。总共，2354 例（37.6%）患者衰弱指数 1 级（FI≤0.210；即无衰弱），2413 例（38.6%）衰弱指数 2 级（FI 0.211-0.310；即更衰弱），1491 例（23.8%）衰弱指数 3 级（FI≥0.311；即最衰弱）。衰弱程度越高，主要终点的发生率越高（每 100 人年）：FI 1 级为 6.3（95%CI 5.7-7.1）；FI 2 级为 8.3（7.5-9.1）；FI 3 级为 13.4（12.1-14.7；<0.001）。达格列净（作为风险比）对 FI 1 级至 3 级的主要终点的影响分别为 0.85（95%CI 0.68-1.06）、0.89（0.74-1.08）和 0.74（0.61-0.91）（=0.40）。尽管衰弱程度较高的患者基线时堪萨斯城心肌病问卷评分较差，但他们的改善程度大于衰弱程度较轻的患者：在 FI 1 级，达格列净治疗 4 个月时堪萨斯城心肌病问卷整体评分的安慰剂校正改善为 0.3（95%CI -0.9 至 1.4）；在 FI 2 级为 1.5（0.3-2.7）；在 FI 3 级为 3.4（1.7-5.1；=0.021）。虽然衰弱程度较高的患者不良反应和停药更常见，但无论虚弱程度如何，达格列净的不良反应和停药均不比安慰剂更常见。
在 DELIVER 中，衰弱很常见，且与预后不良相关。达格列净的获益在研究的衰弱范围内是一致的。达格列净改善健康相关生活质量的作用出现较早，且在衰弱程度较高的患者中更为显著。
