沙库巴曲缬沙坦与缬沙坦对射血分数保留心力衰竭女性与男性患者的影响：PARAGON-HF 研究的见解。
Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.
机构信息
BHF Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M., A.M.J., P.S.J.).
National Heart Center Singapore and Duke-National University of Singapore (C.S.P.L.).
出版信息
Circulation. 2020 Feb 4;141(5):338-351. doi: 10.1161/CIRCULATIONAHA.119.044491. Epub 2019 Nov 17.
BACKGROUND
Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men.
METHODS
In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes.
RESULTS
Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59-0.90) in women and 1.03 (95% CI, 0.84-1.25) in men ( interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men.
CONCLUSIONS
As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding.
CLINICAL TRIAL REGISTRATION
https://www.clinicaltrials.gov. Unique identifier: NCT01920711.
背景
与射血分数降低的心力衰竭不同，射血分数保留的心力衰竭（心力衰竭的主要表型在女性中更为常见）尚无被批准的治疗方法。因此，女性的心力衰竭治疗缺口比男性更大。
方法
在 PARAGON-HF 试验（射血分数保留的心力衰竭中 ARNI 与 ARB 全球结局的前瞻性比较）的预先设定亚组分析中，我们根据性别检查了结果，该试验比较了沙库巴曲缬沙坦和缬沙坦在射血分数保留的心力衰竭患者中的疗效。主要终点是心力衰竭首次住院和再住院以及心血管原因死亡的复合终点。我们还报告了次要疗效和安全性结局。
结果
共有 2479 名女性（51.7%）和 2317 名男性（48.3%）被随机分组。女性年龄较大，肥胖、冠心病、估算肾小球滤过率和 N 末端 B 型利钠肽（NT-proBNP）水平较低。在主要终点方面，沙库巴曲缬沙坦与缬沙坦的比值比在女性中为 0.73（95%CI，0.59-0.90），在男性中为 1.03（95%CI，0.84-1.25）（交互作用=0.017）。沙库巴曲缬沙坦的获益归因于心力衰竭住院率的降低。沙库巴曲缬沙坦在女性和男性中改善纽约心脏协会心功能分级和肾功能的作用相似，而在女性中改善堪萨斯城心肌病问卷临床综合评分的作用小于男性。沙库巴曲缬沙坦与缬沙坦的不良事件差异在女性和男性中相似。
结论
与缬沙坦相比，沙库巴曲缬沙坦似乎能更显著降低女性心力衰竭住院的风险，而治疗效果的可能存在性别相关的差异有几种潜在的解释，但本研究并没有为这一发现提供明确的机制基础。
Zotero 插件