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Evidence summaries

Vitamin K for Improved Anticoagulation Control in Patients Receiving Warfarin

Vitamin K supplementation (150 micrograms phytomenadione per os) may improve the INR stability of the vitamin K antagonist warfarin in patients with existing INR instability. Level of evidence: "C"

The quality of evidence is downgraded by study limitations (unclear allocation concealment), and by imprecise results (few patients).

Vitamin K (phytomenadione) supplementation (150 mcg) is suggested to improve anticoagulation control in patients receiving warfarin with poor INR stability but good medication compliance and for whom direct oral anticoagulants (DOACs) are not suitable.

Summary

A Cochrane review [Abstract] 1 included 2 studies with a total of 100 subjects. One study included 70 patients with atrial fibrillation anticoagulated with warfarin for thromboembolic prophylaxis (target INR 2 to 3) but deemed to have poor control. They were randomised to 6 months of either 150 micrograms (mcg) vitamin K1 (phytomenadione) daily supplementation or matched placebo. The other study identified 50 patients on warfarin therapy with high variability in their INR levels, but randomised 30 participants to receive supplemented oral vitamin K (175 mcg) daily versus placebo for 6 months.

The first study 2 found that he addition of 150 mcg oral vitamin K1 (phytomenadione) resulted in a significantly greater decrease in standard deviation of INR compared with placebo (0.24 ± 0.14 vs 0.11 ± 0.18; P < 0.001) and a significantly greater increase in percentage time within target INR range (table T1). Anticoagulation control improved in 33 of 35 patients receiving vitamin K supplementation; of these, 19 fulfilled criteria for having stable control of anticoagulation. Only 24 of 33 patients receiving placebo demonstrated some degree of improvement, with only 7 patients fulfilling the criteria for having stable control. Daily warfarin dose requirements in patients receiving vitamin K supplementation increased from 3.8 ± 1.6 mg at day 0 to 4.4 ± 1.8 mg at day 7 one week after the study started.

Anticoagulation control prior to and during the intervention period between the vitamin K- and placebo-treated groups.

OutcomeVitamin K groupPlacebo group
Before studyIntervention periodDifferenceBefore studyIntervention periodDifference
INR time in range, %59 ± 2087 ± 1428 ± 2063 ± 1878 ± 1715 ± 20
Significant difference between the vitamin K and placebo groups (P < 0.01).
The second study (n=30) reported that vitamin K supplementation did not significantly improve the stability of anticoagulation. This study was an abstract only, and communication with the corresponding author confirmed that no further data or publications were available. Neither study reported any adverse events, such as thromboembolic events, haemorrhage, or death from the addition of vitamin K supplementation.

A multi-centre RCT 3 included subjects on chronic warfarin therapy and compared oral vitamin K 150 mcg daily or placebo for a total of 6 months after a 1-month run in period. There was no significant difference in the final time in therapeutic range (TTR) between the two groups (65.1% vs 66%, p=0.8). Mean TTR in both low-dose oral vitamin K (LDVK) and placebo groups were statistically increased compared with prior to the study. The number of INR excursions (INR <1.5 or >4.5) were significantly decreased in the LDVK group (9.4% and 5.4%; absolute difference [pre- minus post-] 4%, 95% CI 2 to 6%, p<0.001).

Clinical comments

Daily warfarin dose required may increase during the first week of vitamin K supplementation.

Note

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    References

    • Mahtani KR, Heneghan CJ, Nunan D et al. Vitamin K for improved anticoagulation control in patients receiving warfarin. Cochrane Database Syst Rev 2014;(5):CD009917. [PubMed]
    • Sconce E, Avery P, Wynne H et al. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood 2007;109(6):2419-23. [PubMed]
    • Boonyawat K, Wang L, Lazo-Langner A, et al. The effect of low-dose oral vitamin K supplementation on INR stability in patients receiving warfarin. A randomised trial. Thromb Haemost 2016;116(3):480-5 [PubMed]

    Primary/Secondary Keywords