Heart failure can involve multiple factors, but heart muscle scarring is thought to be an important contributing factor in up to two-thirds of patients with HFpEF.
Use of the antifibrotic drug pirfenidone resulted in a significant reduction in a marker of heart muscle scarring for patients with heart failure with preserved ejection fraction (HFpEF) compared to placebo, according to findings from an early-phase trial presented at the American College of Cardiology's 70th Annual Scientific Session.
Approximately half of patients with heart failure have HFpEF, where the forward pumping function of the heart, or ejection fraction, is normal. Heart failure can involve multiple factors, but heart muscle scarring is thought to be an important contributing factor in up to two-thirds of patients with HFpEF. According to the authors of the study, the current trial suggests clinicians could one day use a personalized approach to prevent or reverse scarring in those individuals and slow the progression of heart failure.
“Observational data suggests that heart muscle scarring, or fibrosis, is an important disease process for heart failure prognosis,” said Chris Miller, MD, a cardiologist and National Institute for Health Research Clinician Scientist at the University of Manchester and Manchester University NHS Foundation Trust, in a prepared statement. “With cardiac MRI, we were able to select a group of patients in whom fibrosis appears to be important and then reduce that scarring. While further investigation is needed, it suggests that fibrosis is an effective treatment target.”
Pirfenidone is currently approved by the FDA for adult patients with idiopathic lung fibrosis, which is scarring in the lungs that impairs breathing. The drug is thought to work by inhibiting biological processes involved in scar formation, though the exact mechanism of action has yet to be established. Preclinical studies suggest pirfenidone can both reduce scar tissue formation and reduce existing scarring in the heart.
The researchers enrolled patients with heart failure, an ejection fraction of 45% or higher, and elevated natriuretic peptides, which are markers of fluid retention. These patients underwent cardiac MRI scanning, and those who had evidence of scarring in the heart muscle, as indicated by an extracellular volume of 27% or greater, were randomly assigned to take pirfenidone or a placebo daily. A total of 94 participants were randomized, with 47 in each treatment group.
After 1 year, patients underwent a second MRI scan to measure the change in heart muscle extracellular volume, the primary endpoint of the study. Extracellular volume declined by 1.21% on average in patients who took pirfenidone compared with those receiving placebo, which is likely to be clinically significant, according to the investigators.
“Based on the data we have from previous observational studies, this amount of change in fibrosis could translate into a significant reduction in death and hospitalization for heart failure, but further work is needed to determine this,” Miller said.
The study also found evidence that fluid retention, measured using natriuretic peptides, improved in patients who took pirfenidone compared to those receiving placebo.
“The associated reduction in natriuretic peptides provides support for heart scarring having a causal role in heart failure and being an efficacious therapeutic target,” Miller said. “Hopefully this work can lead to further development of therapeutics that target heart fibrosis and scarring, and a phase three trial to see if pirfenidone improves patient outcomes.”
Pirfenidone reduces scar tissue in patients with heart failure [news release]. EurekAlert; May 17, 2021. Accessed May 18, 2021. https://www.eurekalert.org/pub_releases/2021-05/acoc-prs051721.php