Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Manchester University NHS Foundation Trust, Manchester, UK.
Nat Med. 2021 Aug;27(8):1477-1482. doi: 10.1038/s41591-021-01452-0. Epub 2021 Aug 12.
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.
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预后相关。口服抗纤维化药物吡非尼酮没有血液动力学作用，其是否对 HFpEF 的治疗有效且安全尚不清楚。在这项双盲、2 期临床试验（NCT02932566）中，我们纳入了射血分数为 45%或更高且利钠肽水平升高的心力衰竭患者。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（定义为心肌细胞外容积为 27%或更高）被随机分配接受吡非尼酮或安慰剂治疗 52 周。47 例患者被随机分配到吡非尼酮组和安慰剂组。主要结局是从基线到 52 周时心肌细胞外容积的变化。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），达到了预设的主要结局。吡非尼酮组 12 例（26%）患者和安慰剂组 14 例（30%）患者发生了 1 次或多次严重不良事件。吡非尼酮组最常见的不良事件是恶心、失眠和皮疹。总之，在 HFpEF 合并心肌纤维化患者中，吡非尼酮治疗 52 周可减少心肌纤维化。吡非尼酮对 HFpEF 患者的疗效需要在未来的试验中得到证实。
