Treatment Adherence in a Randomized Controlled Trial of Pirfenidone in HFpEF: Determinants and Impact on Efficacy.

Objectives: Medication adherence in patients with heart failure with preserved ejection fraction is unclear. This study sought to evaluate treatment adherence in the Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction (PIROUETTE) trial.
Methods and Results: Adherence was evaluated through pill counts and diary cards. Univariable and multivariable regression models were used to assess the relationship between adherence and baseline characteristics. Instrumental variable regression was used to estimate the causal effect of pirfenidone treatment duration on myocardial fibrosis. Complete adherence data were available in 54 of 80 participants completing the trial. Mean adherence to study medication was 94.7% and 96.9% in the pirfenidone and placebo groups, respectively. Each additional day of treatment with pirfenidone resulted in a significant decrease in myocardial extracellular volume (-0.004%; 95% confidence interval: -0.007% to -0.001%; P = 0.007). Associations with adherence included older age, higher symptom burden, lower body weight, and smaller right ventricular size.
Conclusion: Adherence to study medication in the PIROUETTE trial was very high among patients for whom complete adherence data were available. Importantly, each additional day of treatment reduced myocardial fibrosis. Potential predictors of adherence were identified. Implementation of improved methods for assessing adherence is required.
Competing Interests: Disclosures CAM has served on advisory boards for Novartis, Boehringer Ingelheim, Lilly Alliance, and AstraZeneca, serves as an advisor for HAYA Therapeutics and PureTech Health and has received research support from Amicus Therapeutics, Guerbet Laboratories, Roche, and Univar Solutions.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)