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Patients with heart failure with preserved ejection fraction who took the antifibrotic drug Pirfenidone ( Esbriet ) saw a significant reduction in a marker of heart muscle scarring compared with patients who received a placebo, based on findings from an early-phase trial.

Observational data suggests that heart muscle scarring, or fibrosis, is an important disease process for heart failure prognosis.
With cardiac MRI, researchers 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 for treating adults with idiopathic lung fibrosis, or scarring in the lungs that makes it hard to breathe. While the mechanism of action has not been fully established, the drug is thought to work by inhibiting biological processes involved in scar formation.
Preclinical studies have suggested Pirfenidone can both reduce scar tissue formation and reduce existing scarring in the heart.

Researchers enrolled patients with heart failure, an ejection fraction of 45% or higher and elevated natriuretic peptides ( markers of fluid retention ).
Eligible patients underwent cardiac MRI scanning. 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.
In total, 94 patients were randomized, with 47 assigned to each treatment group.

At one year, patients underwent a second cardiac MRI to measure change in heart muscle extracellular volume, the primary endpoint.
Extracellular volume declined by 1.21% on average in patients who took Pirfenidone compared with those receiving placebo.

The study also found evidence that fluid retention, measured using natriuretic peptides, improved in patients who took Pirfenidone compared to those receiving placebo.

The most common adverse events were nausea, insomnia and rash. ( Xagena2021 )

Source: American College of Cardiology's 70th Annual Scientific Session, 2021