Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction
Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction
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DOI：
10.1016/j.jacc.2022.06.037
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发表时间：
2022-09-12
影响因子：
24
通讯作者：
McMurray, John J., V
中科院分区：
文献类型：
--
作者：
Butt, Jawad H.;Dewan, Pooja;McMurray, John J., V
背景虚弱是一个越来越普遍的问题，虚弱的患者不太可能接受新的药物治疗，因为风险-收益情况被认为不如非虚弱的患者。目的研究在Paragon-HF(ARNI与ARB的前瞻性比较)试验中，4796例射血分数保留的心力衰竭患者中，根据虚弱状况应用萨舒比利/valsartan的疗效。方法采用罗克伍德累积亏损法测量脆弱度。主要终点是完全心力衰竭、住院或心血管死亡。结果4795名患者的脆弱指数(FI)是可计算的。总体而言，45.2%的人有1类脆弱(FI#0.210，不脆弱)，43.5%的人有2类脆弱(FI 0.211-0.310，更脆弱)，11.4%的人有3类脆弱(FI$0.311，最脆弱)。FI级与主要终点之间存在分级关系，与更脆弱相关的风险显著更高(1级：参考；2级比率：2.19[95%CI：1.85-2.60]；3级比率：3.29[95%CI：2.65-4.09])。从FI级最低到FI最高，萨舒比利/valsartan和valsartan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交互作用=0.23)。当FI被作为一个连续变量检验时，与治疗的交互作用对主要结果(P交互作用=0.002)和心力衰竭住院总数(P交互作用和t；0.001)有显著意义，那些最虚弱的人获得了更大的好处。结论在射血分数保留的心力衰竭患者中，虚弱是常见的，并且与较差的预后相关。与valsartan相比，saubitril/valsartan似乎显示出主要终点的降低幅度更大，且易损性增加，尽管当将FI作为分类变量检查时，这一点并不显著。(ARNI与ARB在射血分数保留的心力衰竭中的全球预后的前瞻性比较[Paragon-HF]；NCT01920711)(C)2022年提交人。由爱思唯尔公司代表美国心脏病学会基金会出版。
BACKGROUND 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. OBJECTIVES 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. METHODS Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death. RESULTS 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-interaction = 0.23). When FI was examined as a continuous variable, the interaction with treatment was significant for the primary outcome (P-interaction = 0.002) and total heart failure hospitalizations (P-interaction < 0.001), with those most frail deriving greater benefit. CONCLUSIONS 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). (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.