Abstract
Purpose
Warfarin-associated coagulopathy commonly occurs in patients undergoing treatment with this anticoagulant. This trial aimed to determine the efficacy of using low-dose orally administered vitamin K1 to lower international normalized ratio (INR) values into the target range in a cohort of Chinese patients with mechanical heart valves.
Methods
This was a double-blind, placebo-controlled, randomized trial. Chinese patients with mechanical heart valves who were undergoing warfarin treatment and who had INR values from 4.0 to 10.0 without bleeding were the subjects of this study. These patients were randomized into two treatment groups and were orally administered either vitamin K1 (2.5 mg) or placebo. Warfarin was discontinued in both groups until INR values were ≤ 2.5. INR values on the day following treatment were the primary study outcome, with INR values on the following days and adverse clinical events over a 3-month follow-up serving as secondary study outcomes.
Results
In total, 80 patients were enrolled in the present study, and 40 patients each were assigned to the placebo and vitamin K1 treatment groups. Patients administered vitamin K1 exhibited a quick reduction in INR values relative to patients administered placebo (29 of 40 [72.5%] vs. 0 of 44 [0%] patients exhibiting INR values from 1.5–2.5 on the day following treatment, respectively, p = 0.000). Lower bleeding incidence was observed among patients administered vitamin K1 relative to those administered placebo during follow-up (4 [10%] vs. 12 [30%] patients, respectively, p = 0.045). There were no instances of thromboembolic complications or warfarin resistance in either group.
Conclusion
Low-dose oral vitamin K1 can be effectively administered to Chinese patients with mechanical heart valves taking warfarin to rapidly reduce elevated INR values.
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Data availability
The datasets generated and/or analyzed during this study are available from the corresponding author on reasonable request.
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Acknowledgments
We are grateful to all staff at the West China Hospital of Sichuan University who participated in the study.
Funding
The project was funded by the National Science and Technology Program during the Twelfth Five-Year Plan Period (Project number: 2011BAI11B18).
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All key questions were voted on by all authors. Heng Zhang drafted the manuscript and undertook the systematic review with Yijun Dong, Xuelian Ao, and Mei Li. Li Dong modified the manuscript.
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The Institutional Review Board of West China Hospital, Sichuan University approved the present study.
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Informed consent was obtained from all individual participants included in the study.
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The authors declare that they have no conflict of interest.
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Heng Zhang is the first author.
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Zhang, H., Li, M., Ao, Xl. et al. Randomized, placebo-controlled trial of orally administered vitamin K1 for warfarin-associated coagulopathy in Chinese patients with mechanical heart valves. Eur J Clin Pharmacol 77, 1333–1339 (2021). https://doi.org/10.1007/s00228-021-03127-8
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DOI: https://doi.org/10.1007/s00228-021-03127-8