Introduction
The prevalence of atrial fibrillation (AF) is two to three times higher in patients with chronic kidney disease (CKD) than in the general population.1-3 This results in a major therapeutic challenge because patients with CKD and AF have an elevated risk of both systemic thromboembolic events and bleeding.4-6Today’s practice guidelines recommend treatment with a direct oral anticoagulant (DOAC) rather than warfarin, when oral anticoagulation therapy (OAC) is indicated in patients with non-valvular atrial fibrillation (NVAF) – including those with stage I-IV CKD.7 Despite the broad dissemination of these guidelines, warfarin remains the OAC of choice in a high proportion of AF patients in general8 and AF patients with moderate or severe CKD in particular.9
Although the landmark randomized controlled trials (RCTs) of DOACs included a low proportion of AF patients with CKD, the results suggested that DOACs are safe and effective in patients with mild-to-moderate CKD (stages I-III CKD, using Cockcroft-Cault formula).10-13 In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (relative to warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD as well as patients on dialysis.14 Recent population-based studies have also examined the effectiveness and safety of DOACs vs. warfarin in AF patients with CKD.15-22 However, few of these studies provided data on (i) the safety and effectiveness of each individual DOAC vs. warfarin, or (ii) the impact of dose selection in patients with stage III CKD on the incidence of stroke, systemic thromboembolic events, bleeding, and death.16,23 We therefore decided to assess and compare the effectiveness and safety of standard-dose rivaroxaban (20 mg once daily), low-dose rivaroxaban (15 mg once daily), standard-dose apixaban (5.0 mg twice daily), low-dose apixaban (2.5 mg twice daily) and warfarin in a representative cohort of AF patients with stage III CKD.