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

Autor: Lewis GA; 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., Dodd S; Department of Health Data Science, University of Liverpool, a Member of Liverpool Health Partners, Liverpool, UK., Clayton D; Liverpool Clinical Trials Centre, University of Liverpool, Institute of Child Health, Alder Hey Children's NHS Foundation Trust, Liverpool, UK., Bedson E; Liverpool Clinical Trials Centre, University of Liverpool, Institute of Child Health, Alder Hey Children's NHS Foundation Trust, Liverpool, UK., Eccleson H; Liverpool Clinical Trials Centre, University of Liverpool, Institute of Child Health, Alder Hey Children's NHS Foundation Trust, Liverpool, UK., Schelbert EB; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; UPMC Cardiovascular Magnetic Resonance Center, Heart and Vascular Institute, Pittsburgh, PA, USA.; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA., Naish JH; Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK., Jimenez BD; Manchester University NHS Foundation Trust, Manchester, UK., Williams SG; Manchester University NHS Foundation Trust, Manchester, UK., Cunnington C; Manchester University NHS Foundation Trust, Manchester, UK., Ahmed FZ; 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., Cooper A; Salford Royal NHS Foundation Trust, Salford, UK., Rajavarma Viswesvaraiah; Stockport NHS Foundation Trust, Stepping Hill Hospital, Stockport, UK., Russell S; East Cheshire NHS Trust, Macclesfield, UK., McDonagh T; King's College Hospital, London, UK., Williamson PR; Department of Health Data Science, University of Liverpool, a Member of Liverpool Health Partners, Liverpool, UK., Miller CA; Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. Christopher.Miller@manchester.ac.uk.; Manchester University NHS Foundation Trust, Manchester, UK. Christopher.Miller@manchester.ac.uk.; Wellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology & Regenerative Medicine, School of Biology, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. Christopher.Miller@manchester.ac.uk.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2021 Aug; Vol. 27 (8), pp. 1477-1482. Date of Electronic Publication: 2021 Aug 12.
DOI: 10.1038/s41591-021-01452-0
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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