Efficacy and safety of dronedarone versus placebo in patients with atrial fibrillation stratified according to renal function: Post hoc analyses of the EURIDIS-ADONIS trials

Munveer Thind, Wojciech Zareba, Dan Atar, Harry J.G.M. Crijns, Jun Zhu, Hui Nam Pak, James Reiffel, Ulf Ludwigs, Mattias Wieloch, John Stewart, Peter Kowey

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Due to the propensity for CKD to occur alongside atrial fibrillation/atrial flutter (AF/AFL), it is essential that AAD safety and efficacy are assessed for patients with CKD. Hypothesis: Dronedarone, an approved AAD, may present a suitable therapeutic option for patients with AF/AFL and concomitant CKD. Methods: EURIDIS-ADONIS (EURIDIS, NCT00259428; ADONIS, NCT00259376) were identically designed, multicenter, double-blind, parallel-group trials investigating AF/AFL control with dronedarone 400 mg twice daily versus placebo (randomized 2:1). In this post hoc analysis, the primary endpoint was time to first AF/AFL. Patients were stratified according to renal function using the CKD-Epidemiology Collaboration equation and divided into estimated glomerular filtration rate (eGFR) subgroups of 30–44, 45–59, 60–89, and ≥90 ml/min. Time-to-events between treatment groups were compared using log-rank testing and Cox regression. Results: At baseline, most (86%) patients demonstrated a mild or mild-to-moderate eGFR decrease. Median time to first AF/AFL recurrence was significantly longer with dronedarone versus placebo for all eGFR subgroups except the 30 to 44 ml/min group, where the trend was similar but statistical power may have been limited by the small population. eGFR stratification had no significant effect on serious adverse events, deaths, or treatment discontinuations. Conclusions: This analysis suggests that dronedarone could be an effective therapeutic option for AF with an acceptable safety profile in patients with impaired renal function.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalClinical Cardiology
Volume45
Issue number1
DOIs
Publication statusPublished - 2022 Jan

Bibliographical note

Funding Information:
Wojciech Zareba has received research grants from Gilead Sciences, LivaNova, Biotronic, and has consulted for AstraZeneca, MyoKardia, Abbott, and Medtronic. Dan Atar has received honoraria from Boehringer‐Ingelheim, Bayer, BMS/Pfizer, AstraZeneca, MSD, Sanofi, Amgen, and Novartis. Jun Zhu has acted as a speaker for Sanofi. J Reiffel has served as an investigator for Medtronic, Janssen, and Sanofi; and as a consultant for Medtronic, Sanofi, Acension, Correvio, and Amarin during the past 12 months. Peter Kowey has served as a consultant for Sanofi. Ulf Ludwigs, Mattias Wieloch, and John Stewart are employees of Sanofi and may hold shares and/or stock options in the company. The remaining authors declare that there are no conflict of interests.

Funding Information:
We thank Wanda Stipek, PharmD, BCPS, (Sanofi) for coordinating the development, facilitating author discussions, and critical review of this manuscript. Editorial assistance was provided by Cam Hubert (PhD) of Fishawack Communications Ltd., part of Fishawack Health, and was funded by Sanofi.

Publisher Copyright:
© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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