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Multicenter Randomized Controlled Trial of Vitamin K Antagonist Replacement by Rivaroxaban with or without Vitamin K2 in Hemodialysis Patients with Atrial Fibrillation: the Valkyrie Study.

  • 2019-11-08
  • Journal of the American Society of Nephrology : JASN 31(1)
    • An S De Vriese
    • Rogier Caluwé
    • Lotte Pyfferoen
    • Dirk De Bacquer
    • Koen De Boeck
    • Joost Delanote
    • Didier De Surgeloose
    • Piet Van Hoenacker
    • Bruno Van Vlem
    • Francis Verbeke

Study Design

Type
Randomized Controlled Trial (RCT)
Sample size
n = 132
Population
132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation
Methods
randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 µg thrice weekly during 18 months
Blinding
Open-label
Duration
18 months
  • Large Human Trial
  • Highly Cited

Background

Vitamin K antagonists (VKAs), although commonly used to reduce thromboembolic risk in atrial fibrillation, have been incriminated as probable cause of accelerated vascular calcification (VC) in patients on hemodialysis. Functional vitamin K deficiency may further contribute to their susceptibility for VC. We investigated the effect of vitamin K status on VC progression in 132 patients on hemodialysis with atrial fibrillation treated with VKAs or qualifying for anticoagulation.

Methods

Patients were randomized to VKAs with target INR 2-3, rivaroxaban 10 mg daily, or rivaroxaban 10 mg daily plus vitamin K2 2000 µg thrice weekly during 18 months. Systemic dp-ucMGP levels were quantified to assess vascular vitamin K status. Cardiac and thoracic aorta calcium scores and pulse wave velocity were measured to evaluate VC progression.

Results

Baseline dp-ucMGP was severely elevated in all groups. Initiation or continuation of VKAs further increased dp-ucMGP, whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group, but remained nevertheless elevated. Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms. All cause death, stroke, and cardiovascular event rates were similar between the groups. Bleeding outcomes were not significantly different, except for a lower number of life-threatening and major bleeding episodes in the rivaroxaban arms versus the VKA arm.

Conclusions

Withdrawal of VKAs and high-dose vitamin K2 improve vitamin K status in patients on hemodialysis, but have no significant favorable effect on VC progression. Severe bleeding complications may be lower with rivaroxaban than with VKAs.

Research Insights

  • Vitamin K2→Improved Vitamin K Status

    whereas levels decreased in the rivaroxaban group and to a larger extent in the rivaroxaban+vitamin K2 group

    Effect
    Beneficial
    Effect size
    Moderate
    Dose
    2000 µg thrice weekly
  • Vitamin K2→Reduced Vascular Calcification Progression

    Changes in coronary artery, thoracic aorta, and cardiac valve calcium scores and pulse wave velocity were not significantly different among the treatment arms.

    Effect
    Neutral
    Effect size
    Small
    Dose
    2000 µg thrice weekly
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