A Randomized Trial Comparing 1 mg Oral Vitamin K with Placebo for the Treatment of Warfarin-associated Coagulopathy in Patients with Mechanical Heart Valves

Abstract number: OR311

Ageno¹ W, Garcia² D, Galli¹ M, Silingardi³ M, Crowther⁴ M

¹¹University of Insubria, Varese, Italy ²²University of New Mexico, Albuquerque, New Mexico, USA ³³Reggio Emilia Hospital, Reggio Emilia, Italy ⁴⁴McMaster University, Hamilton, Ontario, Canada

Background:  Low dose oral vitamin K effectively reduces the INR in patients presenting with warfarin-associated coagulopathy. However, oral vitamin K is rarely used in the community because of concerns about its safety and effectiveness. This fear is particularly prevalent amongst physicians who treat patients with mechanical heart valves because of the concern about the likelihood of producing subtherapeutic INR values, which may be associated with embolism or valve thrombosis.

Methods:  We performed a pilot, placebo-controlled, randomized clinical trial to determine whether the administration of 1 mg oral vitamin K ‘over corrects’ the INR in patients who present with a mechanical heart valve and an unexpected INR of more than 6.0. The primary outcome measure of the study was the proportion of patients in the vitamin K and placebo arms with INR values of <1.8 24 hours after study drug administration. The secondary outcome was the proportion of patients with INR values of >4.5.

Results:  Twenty-nine patients presenting with an INR of more than 6.0 were randomized to receive 1 mg oral vitamin K (mean age 66 years, range 13–88, 16 males), 31 patients received placebo (mean age 63 years, range 30–83, 11 males). Mean INR at study enrolment was 7.22 and 7.73, respectively. After 24 hours, mean INR was 2.99 and 5.23, respectively. The proportion of patients with an INR of <1.8 was 10.3% (95% CI 2.2, 27.3%) in the vitamin K arm and 0% (0, 9.2%) in the placebo arm (P= 0.09). The proportion of patients with an INR of >4.5 was 6.9% in the vitamin K arm and 60% in the placebo arm, OR 0.05 (0.01, 0.29), P= 0.00009.

Discussion:  Oral vitamin K effectively reduces the INR in patients with mechanical heart valves. About 10% of patients will be ‘over-reversed’; further studies are required to determine the safety and effectiveness of oral vitamin K in this setting.