小柯机器人

英国曼切斯特Christopher A. Miller团队完成吡非尼酮治疗射血分数保留型心力衰竭的临床试验。相关论文于2021年8月12日在线发表在《自然—医学》杂志上。

在一项双盲2期试验（NCT02932566）中，研究人员招募了心力衰竭、射血分数为45%或更高、钠尿肽水平升高的患者。符合条件的患者接受了心血管磁共振检查，那些有心肌纤维化证据的患者，定义为心肌细胞外体积达到或超过27%，被随机分配到接受吡非尼酮或安慰剂，为期52周。47名患者被随机分配到吡非尼酮和安慰剂两组。主要结果是心肌细胞外体积的变化，从基线到52周。与安慰剂相比，吡非尼酮减少了心肌细胞外体积（组间差异，-1.21%；95%置信区间，-2.12至-0.31；P=0.009），达到了预定的主要结果。吡非尼酮组的12名患者（26%）和安慰剂组的14名患者（30%）经历了一个或多个严重的不良事件。吡非尼酮组最常见的不良事件是恶心、失眠和皮疹。

总之，在射血分数保留型心力衰竭（HFpEF）和心肌纤维化的患者中，服用吡非尼酮52周可以减少心肌纤维化。吡非尼酮对HFpEF患者的有利影响还需要在未来的试验中得到证实。

据介绍，在HFpEF中，心肌纤维化的发生与不良后果有关。吡非尼酮是一种没有血液动力学效应的口服抗纤维化药物，对于治疗HFpEF是否有效和安全尚不清楚。

附：英文原文

Title: Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial

Author: Lewis, Gavin A., Dodd, Susanna, Clayton, Dannii, Bedson, Emma, Eccleson, Helen, Schelbert, Erik B., Naish, Josephine H., Jimenez, Beatriz Duran, Williams, Simon G., Cunnington, Colin, Ahmed, Fozia Zahir, Cooper, Anne, Rajavarma Viswesvaraiah, Russell, Stuart, McDonagh, Theresa, Williamson, Paula R., Miller, Christopher A.

Issue&Volume: 2021-08-12

Abstract: In heart failure with preserved ejection fraction (HFpEF), the occurrence of myocardial fibrosis is associated with adverse outcome. Whether pirfenidone, an oral antifibrotic agent without hemodynamic effect, is efficacious and safe for the treatment of HFpEF is unknown. In this double-blind, phase 2 trial (NCT02932566), we enrolled patients with heart failure, an ejection fraction of 45% or higher and elevated levels of natriuretic peptides. Eligible patients underwent cardiovascular magnetic resonance and those with evidence of myocardial fibrosis, defined as a myocardial extracellular volume of 27% or greater, were randomly assigned to receive pirfenidone or placebo for 52 weeks. Forty-seven patients were randomized to each of the pirfenidone and placebo groups. The primary outcome was change in myocardial extracellular volume, from baseline to 52 weeks. In comparison to placebo, pirfenidone reduced myocardial extracellular volume (between-group difference, 1.21%; 95% confidence interval, 2.12 to 0.31; P=0.009), meeting the predefined primary outcome. Twelve patients (26%) in the pirfenidone group and 14 patients (30%) in the placebo group experienced one or more serious adverse events. The most common adverse events in the pirfenidone group were nausea, insomnia and rash. In conclusion, among patients with HFpEF and myocardial fibrosis, administration of pirfenidone for 52 weeks reduced myocardial fibrosis. The favorable effects of pirfenidone in patients with HFpEF will need to be confirmed in future trials.

DOI: 10.1038/s41591-021-01452-0

Source: https://www.nature.com/articles/s41591-021-01452-0

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex