BACKGROUND The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).

中文翻译：

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保留射血分数对心力衰竭的血管紧张素-中枢溶素抑制作用。

背景技术在患有心力衰竭的患者中，血管紧张素受体-中性溶酶抑制剂sacubitril-valsartan导致因心力衰竭或因心血管原因死亡的住院风险降低，并且射血分数降低。目前尚不清楚在保留射血分数的心力衰竭患者中，血管紧张素受体-中性溶酶的抑制作用尚不清楚。方法我们随机分配4822例纽约心脏协会（NYHA）II级至IV级心力衰竭，射血分数达45％或更高，利钠肽水平升高和结构性心脏病的患者接受沙比特利-缬沙坦治疗（目标剂量为97 mg的沙库比利与103毫克的缬沙坦每天两次）或缬沙坦（目标剂量160毫克每天两次）。主要结局是因心力衰竭和因心血管原因死亡的全部住院治疗的综合结果。主要结局组成部分，次要结局（包括NYHA类变化，肾功能恶化和堪萨斯城心肌病问卷调查[KCCQ]临床摘要评分[等级，0到100，较高的分数表示较少的症状和身体限制]）和安全性也进行了评估。结果沙屈比尔-缬沙坦组526例患者发生894起主要事件，缬沙坦组557例患者发生1009起主要事件（发生率，0.87； 95％置信区间[CI]，0.75至1.01； P = 0.06）。沙必比尔-缬沙坦组因心血管原因死亡的发生率为8.5％，缬沙坦组为8.9％（危险比，0.95； 95％CI，0.79至1.16）；分别有690例和797例因心力衰竭而住院（比率为0.85； 95％CI为0.72至1.00）。NYHA等级提高15。屈比特尔-缬沙坦组患者为0％，缬沙坦组患者为12.6％（优势比为1.45； 95％CI为1.13至1.86）；肾功能恶化分别为1.4％和2.7％（危险比，0.50； 95％CI，0.33至0.77）。沙必比尔-缬沙坦组在8个月时KCCQ临床总结评分的平均变化高1.0点（95％CI，0.0至2.1）。屈比特尔-缬沙坦组患者低血压和血管性水肿的发生率较高，高钾血症的发生率较低。在12个预先指定的亚组中，有人提出射血分数较低的患者和女性使用沙比特利-缬沙坦可能具有异质性。结论心力衰竭患者的射血分数为45％或更高，因此沙库比尔-缬沙坦并未导致因心力衰竭和心血管原因死亡的总住院率显着降低。（由诺华（Novartis）资助； PARAGON-HF ClinicalTrials.gov编号，NCT01920711。）。