Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial

Abstract

BackgroundIn patients with normal renal function or early stage CKD, the risk-benefit profile of direct oral anticoagulants (DOACs) is superior to that of vitamin K antagonists (VKAs). In patients on hemodialysis, the comparative efficacy and safety of DOACs versus VKAs are unknown.MethodsIn the Valkyrie study, 132 patients on hemodialysis with atrial fibrillation were randomized to a VKA with a target INR of 2–3, 10 mg rivaroxaban daily, or rivaroxaban and vitamin K2 for 18 months. Patients continued the originally assigned treatment and follow-up was extended for at least an additional 18 months. The primary efficacy end point was a composite of fatal and nonfatal cardiovascular events. Secondary efficacy end points were individual components of the composite outcome and all-cause death. Safety end points were life-threatening, major, and minor bleeding.ResultsMedian (IQR) follow-up was 1.88 (1.01–3.38) years. Premature, permanent discontinuation of anticoagulation occurred in 25% of patients. The primary end point occurred at a rate of 63.8 per 100 person-years in the VKA group, 26.2 per 100 person-years in the rivaroxaban group, and 21.4 per 100 person-years in the rivaroxaban and vitamin K2 group. The estimated competing risk–adjusted hazard ratio for the primary end point was 0.41 (95% CI, 0.25 to 0.68; P=0.0006) in the rivaroxaban group and 0.34 (95% CI, 0.19 to 0.61; P=0.0003) in the rivaroxaban and vitamin K2 group, compared with the VKA group. Death from any cause, cardiac death, and risk of stroke were not different between the treatment arms, but symptomatic limb ischemia occurred significantly less frequently with rivaroxaban than with VKA. After adjustment for competing risk of death, the hazard ratio for life-threatening and major bleeding compared with the VKA group was 0.39 (95% CI, 0.17 to 0.90; P=0.03) in the rivaroxaban group, 0.48 (95% CI, 0.22 to 1.08; P=0.08) in the rivaroxaban and vitamin K2 group and 0.44 (95% CI, 0.23 to 0.85; P=0.02) in the pooled rivaroxaban groups.ConclusionsIn patients on hemodialysis with atrial fibrillation, a reduced dose of rivaroxaban significantly decreased the composite outcome of fatal and nonfatal cardiovascular events and major bleeding complications compared with VKA.Clinical Trial registry name and registration number:Oral Anticoagulation in Hemodialysis, NCT03799822

2021 Focused update of the 2017 consensus guidelines of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation

“…Recently, there has been a few studies suggesting that apixaban or rivaroxaban can be a safer alternative to warfarin in those population. [174][175][176][177] There was no difference in the risks of stroke/systemic embolism between apixaban (n = 2351) and warfarin (n = 23,172) (HR 0.88, 95% CI 0.69-1.12), but apixaban was associated with a significantly lower risk of major bleeding (HR 0.72, 95% CI 0.59-0.87). 174 Among patients with nonvalvular AF and stage 4 or 5 CKD or undergoing hemodialysis, rivaroxaban (n = 1896) did not significantly reduce stroke or systemic embolism (HR 0.55, 95% CI 0.27-1.10) or ischemic stroke (HR 0.67, 95% CI 0.30-1.50) alone, but it was associated with a significant reduction of major bleeding by 32% compared with warfarin (n = 4848).…”

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with advanced chronic kidney and liver diseases

“… 30 The use of NOAC in AF patients receiving dialysis is even more difficult and complex. A prospective multicentre RCT, including 132 AF patients receiving dialysis by De Vriese et al ., 31 found that rivaroxaban (10 mg) was associated with fewer cardiovascular events and major bleeding compared to warfarin, but premature and permanent discontinuation of OAC occurred in 25% of patients. However, a retrospective cohort study with meta-analysis reported no additional benefit of NOACs over warfarin regarding effectiveness and safety.…”

Arrhythmias in Chronic Kidney Disease

“…86 There is evidence suggesting that they may be safe in severe renal impairment also, with some reassuring experience in patients receiving renal dialysis. [87][88] A Cochrane review of 12,545 patients assessed the efficacy and safety of DOACs versus warfarin in patients with AF and CKD. Of these, 390 had severe renal impairment (CrCl 15-30 ml/min).…”