Pirfenidone reduced myocardial fibrosis in patients with heart failure with preserved ejection fraction (HFpEF), according to data from the early-phase PIROUETTE trial presented May 17 during ACC.21. While further investigation is needed, it suggests that fibrosis is an effective treatment target, researchers said.

The study enrolled patients with HF, an ejection fraction ≥45% and elevated natriuretic peptides. Eligible patients underwent cardiac MRI assessment for myocardial fibrosis and those with extracellular volume (ECV) ≥27% 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 ECV, the primary endpoint. Findings showed ECV declined by 1.21% on average in those patients who took pirfenidone compared with those receiving placebo.

"Observational data suggest that … fibrosis, is an important disease process for heart failure prognosis," said Chris Miller, MD, the study's lead author. "With cardiac MRI, we were able to select a group of patients in whom fibrosis appears to be important and then reduce that scarring."

The study also found evidence that fluid retention, measured using natriuretic peptides, improved in patients who took pirfenidone compared with 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."

Looking ahead, researchers said their results provide support for the extracellular matrix having a causal role in heart failure and being an efficacious therapeutic target." However, they note that further studies are needed.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ACC Annual Scientific Session, ACC21, Heart Failure, Stroke Volume

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