Reviwer : Dr. Süleyman Çağan Efe

Name of the Study : Pirfenidone in Heart Failure With Preserved Ejection Fraction – PIROUTTE

Published in Congress : ACC 2021

Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689029/pdf/10557_2019_Article_6876.pdf

Background :

Pirfenidone is a drug used in the treatment of idiopathic pulmonary fibrosis with antifibrotic and collagen formation inhibitory effects. It is known that ACE inhibitors and ARBs have beneficial effects on fibrosis, which has an important place in the pathophysiology of heart failure.

Objective :

 In the PIROUETTE study, the effect of pirfenidone active ingredient, which has antifibrotic and collagen formation inhibitory effects, on reducing myocardial fibrosis in patients with HFpEF was investigated.

Method :

The study evaluated the efficacy of pirfenidone, in comparison with placebo in patients with heart failure with preserved ejection fraction (HFpEF). By random sampling in the study design, patients with HFpEF were randomized to the pirfenidone (n = 47) versus placebo (n = 47) arms. The follow-up period of the study was 12 months and the mean patient age was 78 years, 53% of the patients were male and 34% had diabetes. Patients with HFpEF (left ventricular EF ?45%), N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels ?300 pg/ml and extracellular volume ?27% by evaluation with cardiac magnetic resonance imaging (MRI) were included in the study.

Results :

As the primary outcome, the rate of change in myocardial extracellular volume from baseline to 52 weeks was -0.7% in the pirfenidone group and 0.5% in the placebo group (p = 0.009). In addition, diastolic function, 6-minute walking distance and in the Kansas City Cardiomyopathy Questionnaire score no difference was observed.

Conclusion :

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

Interpretations :

High-rate atrial fibrillation is known to be one of the common causes of decompensation in patients admitted to the clinic with HFpEF. It is known that fibrosis is an important factor in the development of atrial fibrillation. Although the long-term results of the study and its effects on rhythm anomalies are not known, it can create future study targets.