Background: Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) on oral anticoagulants (OACs) are at high risk of bleeding. Determinants of major bleeding risk in OAC users with AF and CKD are not well established and available bleeding score systems do not perform well in CKD. This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-5D.

Methods: We conducted a Swedish register-based cohort study including patients with AF and CKD G3-5D on warfarin or direct OACs (DOACs) between 2009 and 2018. Data were collected from high-quality registers including the Swedish Renal Registry and Auricula, a register for AF and OACs. Risk factors for major bleeding were investigated with Cox regression analysis.

Results: Of 2453 included patients, 59% were on warfarin (time in therapeutic range 67%) and 41% on DOACs. Major bleeding rates were 8.9/100 patient-years. Factors associated with increased bleeding risk were glomerular filtration rate category, G5/5D versus G3 {hazard ratio [HR] 1.92 [95% confidence interval (CI) 1.43-2.56]}, previous gastrointestinal bleeding [HR 1.77 (95% CI 1.39-2.25)], previous other bleeding [HR 1.33 (95% CI 1.09-1.62)], congestive heart failure [HR 1.36 (95% CI 1.11-1.68)], male sex [HR 1.28 (95% CI 1.03-1.60)] and vascular disease [HR 1.35 (95% CI 1.01-1.79)].

Conclusion: Patients with AF and G3-5D on OACs are at a high risk of bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding. The present study also shows an association between OAC-associated bleeding and male sex, congestive heart failure and vascular disease. Knowledge about determinants of bleeding in advanced CKD is essential when deciding on when to anticoagulate or not.