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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 4/2019

Open Access 01-08-2019 | Magnetic Resonance Imaging | ORIGINAL ARTICLE

Pirfenidone in Heart Failure with Preserved Ejection Fraction—Rationale and Design of the PIROUETTE Trial

Authors: Gavin A. Lewis, Erik B. Schelbert, Josephine H. Naish, Emma Bedson, Susanna Dodd, Helen Eccleson, Dannii Clayton, Beatriz Duran Jimenez, Theresa McDonagh, Simon G. Williams, Anne Cooper, Colin Cunnington, Fozia Zahir Ahmed, Rajavarma Viswesvaraiah, Stuart Russell, Stefan Neubauer, Paula R. Williamson, Christopher A. Miller

Published in: Cardiovascular Drugs and Therapy | Issue 4/2019

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Abstract

Background

The PIROUETTE (PIRfenidOne in patients with heart failUre and preserved lEfT venTricular Ejection fraction) trial is designed to evaluate the efficacy and safety of the anti-fibrotic pirfenidone in patients with chronic heart failure and preserved ejection fraction (HFpEF) and myocardial fibrosis. HFpEF is a diverse syndrome associated with substantial morbidity and mortality. Myocardial fibrosis is a key pathophysiological mechanism of HFpEF and myocardial fibrotic burden is strongly and independently associated with adverse outcome. Pirfenidone is an oral anti-fibrotic agent, without haemodynamic effect, that leads to regression of myocardial fibrosis in preclinical models. It has proven clinical effectiveness in pulmonary fibrosis.

Methods

The PIROUETTE trial is a randomised, double-blind, placebo-controlled phase II trial evaluating the efficacy and safety of 52 weeks of treatment with pirfenidone in patients with chronic HFpEF (symptoms and signs of heart failure, left ventricular ejection fraction ≥ 45%, elevated natriuretic peptides [BNP ≥ 100 pg/ml or NT-proBNP ≥ 300 pg/ml; or BNP ≥ 300 pg/ml or NT-proBNP ≥ 900 pg/ml if in atrial fibrillation]) and myocardial fibrosis (extracellular matrix (ECM) volume ≥ 27% measured using cardiovascular magnetic resonance). The primary outcome measure is change in myocardial ECM volume. A sub-study will investigate the relationship between myocardial fibrosis and myocardial energetics, and the impact of pirfenidone, using 31phosphorus magnetic resonance spectroscopy.

Discussion

PIROUETTE will determine whether pirfenidone is superior to placebo in relation to regression of myocardial fibrosis and improvement in myocardial energetics in patients with HFpEF and myocardial fibrosis (NCT02932566).
Appendix
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Metadata
Title
Pirfenidone in Heart Failure with Preserved Ejection Fraction—Rationale and Design of the PIROUETTE Trial
Authors
Gavin A. Lewis
Erik B. Schelbert
Josephine H. Naish
Emma Bedson
Susanna Dodd
Helen Eccleson
Dannii Clayton
Beatriz Duran Jimenez
Theresa McDonagh
Simon G. Williams
Anne Cooper
Colin Cunnington
Fozia Zahir Ahmed
Rajavarma Viswesvaraiah
Stuart Russell
Stefan Neubauer
Paula R. Williamson
Christopher A. Miller
Publication date
01-08-2019
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 4/2019
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-019-06876-y

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