Direct oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation and CKD G3-G5D

Lay Summary The arrythmia atrial fibrillation leads to an increased risk of stroke. Anticoagulants reduce the stroke risk in the general population. Direct oral anticoagulants (DOAC) have been proven to be equally (or more) effective and safe as the traditional warfarin. Whether this also applies in patients with chronic kidney disease is poorly investigated. This Swedish observational study compares DOAC and well-managed warfarin regarding the risk of stroke and bleeding in patients with chronic kidney disease. A total of 2453 patients with atrial fibrillation and moderate to advanced chronic kidney disease, including patients on dialysis, are included. DOAC and warfarin treatment are compared using regression models. DOAC treatment is associated with 30% lower risk of major bleeding compared with warfarin. The stroke risk is comparable between the treatments. This reiterates the results of previous studies, for the first time with a well-managed warfarin comparison group. Randomized controlled studies are needed to confirm the results. Background The use of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD) including dialysis is growing. Several studies have shown favorable results of DOAC compared with warfarin regarding bleeding risk but no difference in stroke protection. However, these studies had poor time in therapeutic range (TTR), in the warfarin comparison group. Methods This was a Swedish national cohort study investigating the risk of ischemic stroke and major bleeding on DOAC compared with warfarin in patients with NVAF, glomerular filtration rate category 3-5D (G3-G5D), kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality national healthcare registries including the Swedish Renal Registry, AuriculA (the Swedish national quality register for AF and anticoagulation) and The Stroke Register. Results At enrolment, of 2453 patients 59% were treated with warfarin (mean TTR 67%) and 41% with DOAC. Overall, 693 (28.3%) had G3, 1113 (45.4%) G4, 222 (9.1%) G5 and 425 (17.3%) G5D. DOAC compared with warfarin showed lower hazard of major bleeding [hazard ratio 0.71 (95% confidence interval 0.53-0.96)] but no difference in ischemic stroke risk. Mortality was increased during DOAC treatment [1.24 (1.01-1.53)], presumably not a causal association since fewer fatal bleedings occurred on DOAC. Conclusions DOAC treatment, compared with warfarin, is associated with almost 30% lower risk of bleeding in patients with NVAF and CKD G3-G5D. The stroke risk is comparable between the treatments. This is the first study comparing DOAC and well-managed warfarin (TTR 67%) in advanced CKD. Ongoing and planned randomized controlled trials need to confirm the possible benefit of DOAC.