Association of Warfarin Initiation to Outcomes of Late-Stage ChronicKidney Disease Patients with Incident Atrial Fibrillation

Objective: The clinical benefit of warfarin therapy for thromboprophylaxis after incident atrial fibrillation (AF) diagnosis in late-stage chronic kidney disease (CKD) patients transitioning to dialysis is unknown. The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of AF in late-stage CKD patients transitioning to dialysis. Methods: In this retrospective cohort analysis, the study population was a national cohort of 22,771 US veterans with incident end stage renal disease (ESRD) who developed incident AF prior to initiating renal replacement therapy. We examined the association of warfarin therapy following the diagnosis of incident AF with ischemic-cerebrovascular accidents (CVA) (ischemic stroke or transient ischemic attack), ischemic-CVA related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event related hospitalizations and post-dialysis all-cause mortality in multivariable adjusted Cox regression analyses adjusting for demographic characteristics and comorbidities. Results: The mean (SD) age of the cohort was 73.5±8.8 years, 13% were African American and the mean CHA2DS2-VASc score was 5.7±2.1. Among overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow up period. The hazard ratios (95% confidence intervals) for ischemic-CVA, bleeding events and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97) compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic-CVA and bleeding event related hospitalizations also. Conclusions: In late-stage CKD patients transitioning to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events, but lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in advanced CKD patients with incident AF. Graphical Abstract Summary for use on social media (Twitter): The clinical benefit of warfarin therapy for thromboprophylaxis after incident atrial fibrillation (AF) diagnosis in late-stage chronic kidney disease (CKD) patients transitioning to dialysis is unknown. Our study from a national cohort of veteran population suggest that warfarin use in advanced CKD is associated with higher risk of ischemic and bleeding events, but lower risk of mortality after dialysis transition. Condensed Abstract The clinical benefit of warfarin therapy for thromboprophylaxis after incident atrial fibrillation (AF) diagnosis in late-stage chronic kidney disease (CKD) patients transitioning to dialysis is unknown. The present study from a national cohort of US veterans evaluates the efficacy and safety of warfarin initiation following the diagnosis of AF in late-stage CKD patients transitioning to dialysis. Our results suggest that warfarin use in advanced CKD is associated with higher risk of ischemic and bleeding events, but lower risk of mortality after end stage renal transition transition. Agarwal et al. Page 2 JACC Clin Electrophysiol. Author manuscript; available in PMC 2021 December 14. A uhor M anscript