Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial
Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial
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DOI：
10.1038/s41591-021-01452-0
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发表时间：
2021-08-12
期刊：
影响因子：
82.9
通讯作者：
Miller, Christopher A.
中科院分区：
文献类型：
--
作者：
Lewis, Gavin A.;Dodd, Susanna;Miller, Christopher A.
在射血分数保留的心力衰竭（HFpEF）中，心肌纤维化的发生与不良结局相关。吡非尼酮是一种无血流动力学效应的口服抗纤维化药物，其治疗HFpEF的有效性和安全性尚不清楚。在这项双盲、2期试验（NCT 02932566）中，我们招募了心力衰竭、射血分数≥ 45%和利钠肽水平升高的患者。符合条件的患者接受心血管磁共振检查，有心肌纤维化证据的患者（定义为心肌细胞外体积≥ 27%）被随机分配接受吡非尼酮或安慰剂治疗52周。将47例患者随机分配至吡非尼酮组和安慰剂组。主要结局是心肌细胞外容积从基线至52周的变化。与安慰剂相比，吡非尼酮降低了心肌细胞外容积（组间差异，-1.21%; 95%置信区间，-2.12至-0.31; P = 0.009），符合预定义的主要结局。吡非尼酮组12例患者（26%）和安慰剂组14例患者（30%）发生了1起或多起严重不良事件。吡非尼酮组最常见的不良事件为恶心、失眠和皮疹。总之，在HFpEF和心肌纤维化患者中，吡非尼酮给药52周可减少心肌纤维化。吡非尼酮对HFpEF患者的有利作用需要在未来的试验中证实。
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.