Pirfenidone in Heart Failure With Preserved Ejection Fraction - PIROUTTE

Contribution To Literature:

The PIROUETTE trial showed that pirfenidone was beneficial at reducing myocardial fibrosis among patients with HFpEF.


The goal of the trial was to evaluate pirfenidone, an antifibrotic agent, compared with placebo among patients with heart failure with preserved ejection fraction (HFpEF).

Study Design

  • Randomized
  • Parallel

Patients with HFpEF were randomized to pirfenidone (n = 47) versus placebo (n = 47).

  • Total number of enrollees: 94
  • Duration of follow-up: 12 months
  • Mean patient age: 78 years
  • Percentage female: 47%
  • Percentage with diabetes: 34%

Inclusion criteria:

  • HFpEF (left ventricular EF [LVEF] ≥45%)
  • N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml
  • Extracellular volume ≥27%, as assessed by cardiac magnetic resonance imaging (MRI)

Principal Findings:

The primary outcome, change in myocardial extracelluar volume (%) from baseline to 52 weeks, was -0.7 in the pirfenidone group compared with 0.5 in the placebo group (p = 0.009).

Secondary outcomes:

  • No difference in diastolic function
  • No difference in 6-minute walk distance
  • No difference in Kansas City Cardiomyopathy Questionnaire summary score


Among patients with HFpEF, pirfenidone appeared to be beneficial. This medication was associated with a modest reduction in myocardial fibrosis, as assessed by cardiac MRI, compared with placebo. The clinical significance of this finding is unknown.


Presented by Dr. Christopher Miller at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 17, 2021.

Clinical Topics: Anticoagulation Management, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging

Keywords: ACC21, ACC Annual Scientific Session, Cardiomyopathies, Diastole, Fibrosis, Geriatrics, Heart Failure, Magnetic Resonance Imaging, Natriuretic Peptide, Brain, Peptide Fragments, Stroke Volume

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