British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
J Am Coll Cardiol. 2022 Sep 20;80(12):1130-1143. doi: 10.1016/j.jacc.2022.06.037. Epub 2022 Aug 29.
Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk-benefit profile is perceived to be less favorable than in nonfrail patients.
This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.
Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death.
A frailty index (FI) was calculable in 4,795 patients. In total, 45.2% had class 1 frailty (FI ≤0.210, not frail), 43.5% had class 2 frailty (FI 0.211-0.310, more frail), and 11.4% had class 3 frailty (FI ≥0.311, most frail). There was a graded relationship between FI class and the primary endpoint, with a significantly higher risk associated with greater frailty (class 1: reference; class 2 rate ratio: 2.19 [95% CI: 1.85-2.60]; class 3 rate ratio: 3.29 [95% CI: 2.65-4.09]). The effect of sacubitril/valsartan vs valsartan on the primary endpoint from lowest to highest FI class (as a rate ratio) was: 0.98 [95% CI: 0.76-1.27], 0.92 [95% CI: 0.76-1.12], and 0.69 [95% CI: 0.51-0.95]), respectively (P = 0.23). When FI was examined as a continuous variable, the interaction with treatment was significant for the primary outcome (P = 0.002) and total heart failure hospitalizations (P < 0.001), with those most frail deriving greater benefit.
Frailty was common in heart failure with preserved ejection fraction and associated with worse outcomes. Compared with valsartan, sacubitril/valsartan seemed to show a greater reduction in the primary endpoint with increasing frailty, although this was not significant when FI was examined as a categorical variable. (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
衰弱是一个日益普遍的问题，衰弱患者接受新的药物治疗的可能性较小，因为其风险效益比被认为不如非衰弱患者有利。
本研究旨在探讨沙库巴曲缬沙坦在 PARAGON-HF（心力衰竭伴射血分数保留的前瞻性比较 ARNI 与 ARB 全球结局试验）试验中 4796 例射血分数保留心力衰竭患者中的疗效与衰弱状态的关系。
采用 Rockwood 累积缺陷法评估衰弱情况。主要终点为心力衰竭住院或心血管死亡的总发生率。
在可计算衰弱指数（FI）的 4795 例患者中，45.2%的患者为 1 级衰弱（FI≤0.210，无衰弱），43.5%的患者为 2 级衰弱（FI 0.211-0.310，衰弱程度增加），11.4%的患者为 3 级衰弱（FI≥0.311，最衰弱）。FI 分级与主要终点之间存在分级关系，衰弱程度越高，风险越高（1 级：参考；2 级率比值：2.19[95%CI：1.85-2.60]；3 级率比值：3.29[95%CI：2.65-4.09]）。从最低到最高 FI 级（按率比值），沙库巴曲缬沙坦与缬沙坦对主要终点的影响分别为：0.98[95%CI：0.76-1.27]、0.92[95%CI：0.76-1.12]和 0.69[95%CI：0.51-0.95]（P=0.23）。当 FI 作为连续变量进行检查时，治疗与主要结局之间的交互作用具有统计学意义（P=0.002）和心力衰竭住院总发生率（P<0.001），最衰弱的患者获益更大。
射血分数保留的心力衰竭患者中衰弱较为常见，且与不良结局相关。与缬沙坦相比，沙库巴曲缬沙坦似乎在衰弱程度增加时对主要终点有更大的降低作用，尽管当 FI 作为分类变量进行检查时，这并不显著。（心力衰竭伴射血分数保留的前瞻性比较 ARNI 与 ARB 全球结局试验[PARAGON-HF]；NCT01920711）。
