Compared with vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) are associated with a superior risk-benefit profile in patients with normal renal function or early-stage chronic kidney disease (CKD). Results from the Valkyrie trial recently published in the Journal of the American Society of Nephrology showed that a low dose of the DOAC rivaroxaban decreased fatal and nonfatal cardiovascular (CV) events and major bleeding complications compared with VKAs in patients with atrial fibrillation (AF) who are on hemodialysis.
These results suggest that VKAs should be avoided in patients with AF on hemodialysis, and further support the use of DOACs in patients on hemodialysis with nonvalvular AF, a position that has been historically considered controversial, said lead investigator An S. De Vriese, MD, PhD, of AZ Sint-Jan Brugge and Ghent University in Belgium.
She added that, prior to this study, there has been little published data on the safety and efficacy of rivaroxaban and apixaban in this patient population and no published randomized-controlled trials have compared VKAs and DOACs in this setting. “Rivaroxaban, and in particular apixaban, are increasingly used in hemodialysis patients with AF, despite a lack of validated dosing guidelines in the hemodialysis population,” said Dr. De Vriese.
The Valkyrie study randomized 132 patients with AF who were on hemodialysis to one of the following treatment arms:
- VKA with a target international normalized ratio of 2-3 (n=44)
- rivaroxaban 10 mg daily (n=46)
- rivaroxaban and vitamin K2 (n=42)
Treatment lasted for 18 months, after which patients were eligible to enter an extension follow-up study for at least another 18 months.
Additional secondary efficacy endpoints included individual components of the primary composite outcome and all-cause death. The safety endpoints of the study included life-threatening, major, and minor bleeding events.
The median ages of patients in the VKA, rivaroxaban, and rivaroxaban plus vitamin K2 groups were 80.3, 79.9, and 79.6 years, respectively. Most patients in each group were men and most patients had at least one CV risk factor (including diabetes, a history of acute myocardial infarction, congestive heart failure, and preexisting vascular disease).
During a median follow-up period of 1.88 years, approximately 25% of patients prematurely and permanently discontinued anticoagulation: 31.8% of patients in the VKA group and 21.6% of patients in the pooled rivaroxaban groups.
The composite primary endpoint of fatal and nonfatal CV events occurred more often in the VKA arm than in the rivaroxaban arm (63.8 vs. 26.2 events per 100 person-years) compared with the rivaroxaban group (26.2 events per 100 person-years) and the rivaroxaban and vitamin K2 group (21.4 events per 100 person-years). Compared with the VKA group, the risk-adjusted hazard ratio (HR) for the primary endpoint was 0.41 in participants in the rivaroxaban group (p=0.0006) and 0.34 in the rivaroxaban and vitamin K2 group (p=0.0003).
Investigators also found no difference between the treatment groups in terms of any-cause death, cardiac death, or risk of stroke. The investigators observed less frequent occurrences of symptomatic limb ischemia in the pooled rivaroxaban groups (n=11) than with VKA (n=20).
In an analysis adjusted for the competing risk of death, the HRs for life-threatening and major bleeding (vs. VKA) were 0.39 in the rivaroxaban group (p=0.03) and 0.48 in the rivaroxaban and vitamin K2 group (p=0.08). Across the pooled rivaroxaban groups, the HR was 0.44 (p=0.02).
“In patients with normal renal function or early-stage CKD, the burden of evidence shows that DOACs have a superior benefit-risk profile as compared with VKA,” said Dr. De Vriese. “However, we learned from experience with cardiologic device and pharmacologic interventions that data from patients without advanced CKD should not be translated uncritically to patients on dialysis.” She added that these results suggest a net clinical benefit with DOAC compared to VKA among patients receiving hemodialysis.
This study is limited by its lack of a placebo arm, which Dr. De Vriese said should be addressed by conducting a randomized controlled trial of rivaroxaban versus no anticoagulation in the hemodialysis population.
Study authors report no relevant conflicts of interest.
De Vriese AS, Caluwé R, Van Der Meersch H, De Boeck K, De Bacquer D. Safety and efficacy of vitamin K antagonists versus rivaroxaban in hemodialysis patients with atrial fibrillation: A multicenter randomized controlled trial [published online ahead of print, 2021 Mar 22]. J Am Soc Nephrol. doi: 10.1681/ASN.2020111566.