PIROUETTE: Pirfenidone reduces myocardial fibrosis in patients with HFpEF
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In patients with HF with preserved ejection fraction, pirfenidone was associated with reduction in myocardial fibrosis compared with placebo, according to a presentation at the American College of Cardiology Scientific Session.
“The primary outcome, which was change in myocardial extracellular from baseline to week 52 measured using cardiac MRI, was significant, with a greater reduction in those assigned to pirfenidone rather than placebo. Among patients HFpEF and myocardial fibrosis, myocardial fibrosis was reduced by treatment with pirfenidone over 52 weeks,” Chris Miller, BSc, MBChB (Hons), MRCP (UK), PhD, a cardiologist and National Institute for Health Research Clinician Scientist at the University of Manchester and Manchester University NHS Foundation Trust, said during a press conference.
Researchers enrolled 94 patients with HF, an ejection fraction of 45% or higher and elevated natriuretic peptides in the PIROUETTE Trial.
Patients underwent cardiac MRI and those who had evidence of scarring in the heart muscle of 27% or greater were randomly assigned daily pirfenidone (mean age, 78 years; 47% women) or placebo (mean age, 81 years; 45% women).
At 52 weeks, extracellular volume declined 0.7% in the pirfenidone group and increased 0.5% in the placebo group (between-group difference, –1.21%; 95% CI, –2.12 to –0.31; P = .009), Miller said.
For each additional 100 capsules of pirfenidone taken, the mean change in extracellular volume at 52 weeks was –0.06%; (95% CI, –0.1 to –.01; P = .01), Miller said at the press conference.
There were no differences in diastolic function, atrial size and function or right ventricular size and function, he said.
According to the researchers, 26% of the participants who took pirfenidone had an adverse event while 30% of the placebo patients experienced one.
“The findings suggested that pirfenidone could have favorable clinical facts in patients with HFpEF, but further trials are necessary to determine the clinical effectiveness and safety,” Miller said at the press conference.
Perspective
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W.H. Wilson Tang, MD
Fibrosis has been a promising therapeutic target for HFpEF, even though the link between therapeutic reduction of fibrosis and improvement in clinical outcomes has not been firmly established.
This British study investigated antifibrotic effects of pirfenidone in HFpEF. Pirfenidone is a drug that is already approved for treating idiopathic pulmonary fibrosis, with promising basic science data targeting profibrotic pathways. In this double-blind, randomized controlled study of 94 patients, pirfenidone was associated with improvement in myocardial extracellular volume, a novel surrogate marker of myocardial fibrosis that is measured by MRI. There were also a number of nonsignificant improvements in clinical endpoints (like N-terminal pro-B natriuretic peptide and 6-minute walk distance) that are perhaps too hard to interpret due to the small sample size. There appeared to be no differences in diastolic function, atrial size and function, or right ventricular size and function, which were similar to our prior case series with serial echocardiogram measurements in patients with idiopathic pulmonary fibrosis.
Nevertheless, with limited treatment for HFpEF, these findings provide some enthusiasm and promise that would need to be confirmed in larger studies.
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Miller C, et al. Late Breaking Clinical Trials IV. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).
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