Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Dec 25, 2023; 12(5): 132-146
Published online Dec 25, 2023. doi: 10.5527/wjn.v12.i5.132
Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease
Sylvie Perreault, Laurie-Anne Boivin Proulx, Aurélie Lenglet, Ziad A Massy, Marc Dorais
Sylvie Perreault, Faculty of Pharmacy, University of Montreal, Quebec, Montreal H3C3J7, Canada
Laurie-Anne Boivin Proulx, Department of Cardiology, Faculty of Medicine, University of Ottawa Heart Institute, Ontario, Ottawa K1Y4W7, Canada
Aurélie Lenglet, Department of Pharmacy, Amiens-Picardie Hospital University Center, Amiens 80000, France
Aurélie Lenglet, Faculty of Pharmacy, MP3CV Laboratory, UR7545, University of Picardie Jules Verne, Amiens 80000, France
Ziad A Massy, Division of Nephrology, University of Paris Ouest -Versailles-Saint-Quentin-en-Yvelines (UVSQ), Villejuif, France., AP-HP Ambroise-Paré Hospital, Boulogne Billancourt/Paris 92104, France
Marc Dorais, StatSciences Inc., Notre-Dame-de-l’Île-Perrot, Quebec, Montreal J7W 3K8, Canada
Author contributions: Perreault S, Boivin-Proulx LA, Lenglet A and Massy ZA contributed equally to concept, writing, and revising of the manuscript; Dorais M contributed to data analysis, figures, and reviewed the manuscript.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Reviewer.
Informed consent statement: As the study used anonymous and pre-existing data, the requirement for the informed consent from patients was waived.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: No data sharing is authorized according to the agreement of the Commission d’accès à l’information that authorizing the study.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sylvie Perreault, BPharm, MSc, PhD, Professor, Faculty of Pharmacy, University of Montreal, No. 2940 Chemin de Polytechnique, Quebec, Montreal H3C3J7, Canada. sylvie.perreault@umontreal.ca
Received: May 19, 2023
Peer-review started: May 19, 2023
First decision: July 19, 2023
Revised: July 26, 2023
Accepted: September 26, 2023
Article in press: September 26, 2023
Published online: December 25, 2023
Processing time: 216 Days and 21.2 Hours
Abstract
BACKGROUND

Randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) included a low proportion of atrial fibrillation (AF) patients with chronic kidney disease (CKD), and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD. In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (vs warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD. But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD. The effectiveness and safety of DOACs in those patients are still subject to debate.

AIM

To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population.

METHODS

A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation. Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards.

RESULTS

A total of 8899 included patients filled out a new oral anticoagulation therapy claim; 3335 for warfarin and 5564 for DOACs. Compared with warfarin, 15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk [Hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.65-0.88] and a similar safety risk (HR 0.94; 95%CI: 0.66-1.35). Apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95%CI: 0.79-1.26) and a lower safety risk (HR 0.65; 95%CI: 0.43-0.99. Although, apixaban 5.0 mg was associated with a better effectiveness (HR 0.76; 95%CI: 0.65-0.88), but a similar safety risk profile (HR 0.94; 95%CI: 0.66-1.35). The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality (HR 0.61; 95%CI: 0.43-0.88).

CONCLUSION

In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Keywords: Atrial fibrillation; Chronic kidney disease; Direct oral anticoagulant; Effectiveness; Safety; Warfarin

Core Tip: Compared to warfarin, rivaroxaban and apixaban appear to be effective and safe in atrial fibrillation patients with stage III chronic kidney disease (CKD) in real world. Rivaroxaban 15 mg and 20 mg presented a similar effectiveness and safety composite risk. However, apixaban 2.5 mg might even have a better safety profile than warfarin, while apixaban 5.0 mg might have a better effectiveness profile than warfarin, to a reduction in deaths. Appropriately sized randomized controlled trials are needed to confirm these findings in stage III CKD patients.