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Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
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Pirfenidone in heart failure with preserved ejection fraction: a randomized phase 2 trial
Gavin A Lewis1,2, Susanna Dodd3, Dannii Clayton4
1Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Nature Medicine
|August 13, 2021
Summary
Pirfenidone effectively reduced myocardial fibrosis in patients with heart failure with preserved ejection fraction (HFpEF). This antifibrotic treatment showed promise for HFpEF patients with fibrosis, warranting further investigation.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Myocardial fibrosis is linked to poor outcomes in heart failure with preserved ejection fraction (HFpEF).
- The efficacy and safety of pirfenidone, an oral antifibrotic, for HFpEF remain unestablished.
Purpose of the Study:
- To evaluate the efficacy and safety of pirfenidone in treating HFpEF patients with myocardial fibrosis.
Main Methods:
- A double-blind, phase 2 trial randomized 94 HFpEF patients with myocardial fibrosis (extracellular volume ≥27%) to pirfenidone or placebo for 52 weeks.
- Cardiovascular magnetic resonance assessed changes in myocardial extracellular volume as the primary outcome.
Main Results:
- Pirfenidone significantly reduced myocardial extracellular volume compared to placebo (difference: -1.21%, P=0.009).
- Serious adverse events were comparable between groups (26% pirfenidone vs. 30% placebo). Common side effects included nausea, insomnia, and rash.
Conclusions:
- Pirfenidone demonstrated efficacy in reducing myocardial fibrosis in HFpEF patients over 52 weeks.
- The antifibrotic effects of pirfenidone in HFpEF require confirmation in larger, future clinical trials.
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