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Vitamin K to Reverse Excessive VKA Anticoagulation

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Brady L. Stein, MD, MHS reviewing

Authors: Khatib R et al. 

Blood Adv 2019 Mar 12

Beyond holding anticoagulation, adding vitamin K did not reduce mortality, bleeding, or thrombosis risks in nonbleeding patients with elevated INRs.

Labile international normalized ratios (INRs) due to drug interactions, dietary changes, and acute illness increase bleeding risks in patients receiving vitamin K antagonists (VKAs). In 2008, clinical practice guidelines were changed to advise against administration of vitamin K in nonbleeding patients with INR elevation.

To assess the effect of combining vitamin K with VKA cessation to reverse excessive anticoagulation in this setting, investigators conducted a meta-analysis of five randomized, controlled trials involving 1074 nonbleeding adults with INRs between 4.5 to 10.0 requiring temporary cessation of VKAs (warfarin in 3 studies, acenocoumarol in 2). At baseline, patients randomized to vitamin K administration versus placebo or observation had similar INRs (between 5.4–8.4 and 5.8–8.1, respectively). Follow-up duration ranged from 7 to 90 days.

Risks for all-cause mortality, major bleeding, and thromboembolism were nonsignificantly greater with vitamin K administration than with placebo or observation (pooled risk ratios, 1.42, 2.43, and 1.29, respectively, with moderate certainty of evidence). The likelihood of reaching INR goal was nonsignificantly greater with vitamin K administration (pooled RR, 1.95, with very low certainty of evidence).

COMMENT

These results demonstrate that nonbleeding patients receiving VKA therapy who have INRs between 4.5 and 10.0 do not benefit from adding vitamin K administration to VKA cessation. In the contemporary era, patients with labile INRs and no contraindications often transition from VKAs to direct oral anticoagulants. However, guidance on managing labile INRs is important in populations that require VKAs, such as those with valvular heart disease or advanced renal disease. The current study was funded by the American Society of Hematology to aid in the development of venous thromboembolism guidelines, which will be welcomed in this setting. As the authors note, however, implementing such guidelines will be a challenge, since both familiarity with and adherence to the prior 2008 recommendations, which are consistent with the current findings, were very low.

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