Randomized, placebo-controlled trial of orally administered vitamin K1 for warfarin-associated coagulopathy in Chinese patients with mechanical heart valves.

2021-03-30
European journal of clinical pharmacology 77(9)
- Heng Zhang
- Mei Li
- Xue-Lian Ao
- Yi-Jun Dong
- Li Dong

PubMed: 33783553
DOI: 10.1007/s00228-021-03127-8

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 80
Population: Chinese patients with mechanical heart valves who were undergoing warfarin treatment and who had INR values from 4.0 to 10.0 without bleeding
Methods: Double-blind, placebo-controlled, randomized trial. 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.
Blinding: Double-blind
Duration: 3-month follow-up
Funding: Unclear

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.

Research Insights

Vitamin K1→Reduced Bleeding Incidence
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).
Effect
Beneficial
Effect size
Moderate
Dose
2.5 mg
Vitamin K1→Reduced International Normalized Ratio
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).
Effect
Beneficial
Effect size
Large
Dose
2.5 mg