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.