Oral vitamin K did not reduce bleeding in patients with excessive anticoagulation after receiving warfarin

Rondina M. — Tue, 16 Jun 2009 00:00:00 GMT

Question

In patients with warfarin-associated coagulopathy, does low-dose oral vitamin K reduce risk for bleeding?

Methods

Design

Randomized placebo-controlled trial. ClinicalTrials.gov NCT00143715.

Allocation

Concealed.*

Blinding

Blinded (patients, clinicians, research coordinators, and outcome adjudicators).*

Follow-up period

90 days.

Setting

14 anticoagulant centers in the USA, Canada, and Italy.

Patients

724 outpatients ≥ 18 years of age (mean age 69 y, 53% men) who attended clinic for routine international normalized ratio (INR) assessment, were receiving warfarin with a target INR of 2.0 to 3.5, were not bleeding, and had an INR between 4.5 and 10.0 in the past 24 hours. Exclusion criteria included life expectancy < 10 days, indication for acute normalization of INR, scheduled discontinuation of warfarin, known bleeding disorder, recent major bleeding, inability to take oral medication or undergo follow-up, contraindication to vitamin K, severe liver disease, thrombolytic therapy within 48 hours, and platelet count < 50 x 10⁹ cells/L.

Intervention

Single-dose oral vitamin K, 1.25 mg (n = 355), or placebo (n = 369).

Outcomes

Any bleeding events at 90 days. Secondary outcomes included major bleeding (fatal bleeding, bleeding requiring transfusion of ≥ 2 units of packed red blood cells or therapeutic intervention, or objectively confirmed bleeding into an enclosed space), objectively confirmed venous or arterial thromboembolism, and death.

Patient follow-up

98% (100% in intention-to-treat analysis).

Main results

At 90 days, oral vitamin K did not reduce bleeding events or major bleeding events and did not cause venous or arterial thromboembolism or death (Table).

Conclusion

In patients with warfarin-associated coagulopathy, oral vitamin K did not reduce bleeding or cause thromboembolism or death.Vitamin K vs placebo in patients with warfarin-associated coagulopathy†OutcomesVitamin KPlaceboAt 90 dRRR (95% CI)NNTAny bleeding15.8%16.3%3% (−35 to 30)Not significantRRI (CI)NNHMajor bleeding2.5%1.1%134% (−23 to 611)Not significantThromboembolism1.1%0.8%39% (−65 to 450)Not significantDeath2.0%1.9%4% (−62 to 181)Not significant†Abbreviations defined in Glossary. RRI, RRR, NNH, NNT, and CI calculated from data in article.

Annals of Internal Medicine: Coagulopathies Topic Collection

Oral vitamin K did not reduce bleeding in patients with excessive anticoagulation after receiving warfarin