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

Lewis, Gavin A, Dodd, Susanna ORCID: 0000-0003-2851-3337, Clayton, Dannii ORCID: 0000-0003-3535-3466, Bedson, Emma, Eccleson, Helen, Schelbert, Erik B, Naish, Josephine H, Jimenez, Beatriz Duran, Williams, Simon G, Cunnington, Colin
et al (show 7 more authors) (2021) Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial. NATURE MEDICINE, 27 (8). 1477-+.

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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.

Item Type: Article
Uncontrolled Keywords: Humans, Pyridones, Treatment Outcome, Time Factors, Aged, Female, Male, Heart Failure
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Clinical Directorate
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 08 Feb 2022 11:34
Last Modified: 18 Jan 2023 21:13
DOI: 10.1038/s41591-021-01452-0
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3148503

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