西地那非对射血分数降低的心力衰竭合并肺动脉高压患者症状及运动能力的影响（SilHF研究）：一项随机安慰剂对照多中心试验

Effects of sildenafil on symptoms and exercise capacity for heart failure with reduced ejection fraction and pulmonary hypertension (the SilHF study): a randomized placebo-controlled multicentre trial.

作者信息

Cooper Trond J, Cleland John G F, Guazzi Marco, Pellicori Pierpaolo, Ben Gal Tuvia, Amir Offer, Al-Mohammad Abdallah, Clark Andrew L, McConnachie Alex, Steine Kjetil, Dickstein Kenneth

机构信息

Stavanger University Hospital, Stavanger, Norway.

National Heart Lung Institute, Imperial College, London, UK.

出版信息

Eur J Heart Fail. 2022 Jul;24(7):1239-1248. doi: 10.1002/ejhf.2527. Epub 2022 Jun 6.

DOI:10.1002/ejhf.2527

PMID:35596935

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9544113/

Abstract

AIMS

Pulmonary hypertension (PHT) may complicate heart failure with reduced ejection fraction (HFrEF) and is associated with a substantial symptom burden and poor prognosis. Sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, might have beneficial effects on pulmonary haemodynamics, cardiac function and exercise capacity in HFrEF and PHT. The aim of this study was to determine the safety, tolerability, and efficacy of sildenafil in patients with HFrEF and indirect evidence of PHT.

METHODS AND RESULTS

The Sildenafil in Heart Failure (SilHF) trial was an investigator-led, randomized, multinational trial in which patients with HFrEF and a pulmonary artery systolic pressure (PASP) ≥40 mmHg by echocardiography were randomly assigned in a 2:1 ratio to receive sildenafil (up to 40 mg three times/day) or placebo. The co-primary endpoints were improvement in patient global assessment by visual analogue scale and in the 6-min walk test at 24 weeks. The planned sample size was 210 participants but, due to problems with supplying sildenafil/placebo and recruitment, only 69 patients (11 women, median age 68 (interquartile range [IQR] 62-74) years, median left ventricular ejection fraction 29% (IQR 24-35), median PASP 45 (IQR 42-55) mmHg) were included. Compared to placebo, sildenafil did not improve symptoms, quality of life, PASP or walk test distance. Sildenafil was generally well tolerated, but those assigned to sildenafil had numerically more serious adverse events (33% vs. 21%).

CONCLUSION

Compared to placebo, sildenafil did not improve symptoms, quality of life or exercise capacity in patients with HFrEF and PHT.

摘要

目的

肺动脉高压（PHT）可能使射血分数降低的心力衰竭（HFrEF）复杂化，并伴有严重的症状负担和不良预后。西地那非是一种磷酸二酯酶-5（PDE-5）抑制剂，可能对HFrEF和PHT患者的肺血流动力学、心脏功能和运动能力产生有益影响。本研究的目的是确定西地那非在HFrEF和PHT间接证据患者中的安全性、耐受性和疗效。

方法与结果

心力衰竭中的西地那非（SilHF）试验是一项由研究者主导的、随机、多国试验，其中通过超声心动图诊断为HFrEF且肺动脉收缩压（PASP）≥40 mmHg的患者按2:1的比例随机分配，接受西地那非（每日三次，每次最多40 mg）或安慰剂。共同主要终点是24周时通过视觉模拟量表评估的患者整体状况改善以及6分钟步行试验结果。计划样本量为210名参与者，但由于西地那非/安慰剂供应和招募问题，仅纳入了69例患者（11名女性，年龄中位数68岁（四分位间距[IQR] 62 - 74岁），左心室射血分数中位数29%（IQR 24 - 35），PASP中位数45（IQR 42 - 55）mmHg）。与安慰剂相比，西地那非未改善症状、生活质量、PASP或步行试验距离。西地那非总体耐受性良好，但分配到西地那非组的患者发生严重不良事件的数量在数值上更多（33%对21%）。