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

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.

Comparison of Antithrombotic Strategies in Chinese Patients in Sinus Rhythm after Bioprosthetic Mitral Valve Replacement: Early Outcomes from a Multicenter Registry in China.

OBJECTIVES: To compare antithrombotic strategies in Chinese patients undergoing bioprosthetic mitral valve implantation discharged in normal sinus rhythm. METHODS: At 28 hospitals in China, 1603 patients were followed for 2991.5 person-years. Adverse event and death rates during five postoperative time intervals (≤ 30, 31-90, 91-180, 181-365, and 366-730 days) were calculated in patients administered warfarin, aspirin, warfarin + aspirin, or neither treatment. RESULTS: Thromboembolic and hemorrhagic events occurred in 22 (0.74/100 patient-years, 95%CI 0.43-1.05) and 28 (0.94/100 patient-years, 95%CI 0.59-1.29) patients, respectively. In the first 3 months post-surgery, warfarin-treated patients had significantly lower rates of thromboembolic events than the aspirin or untreated groups (P = 0.01, P<0.01), and a significantly lower risk of bleeding than the aspirin + warfarin group (P = 0.02). From 91 to 180 days post-surgery, thromboembolism risk was significantly lower in warfarin-treated patients relative to the aspirin-treated and untreated patients (P = 0.04, P = 0.04), but bleeding and overall adverse event rates were similar (P = 1.00). From 181 to 365 days, thromboembolic event rates did not differ significantly between the untreated and anticoagulant-treated groups (P = 1.00). CONCLUSION: Warfarin is the most effective intervention for preventing thromboembolism within 6 months post-bioprosthetic MVR surgery in Chinese patients in sinus rhythm. After 6 months, further warfarin therapy was unnecessary, and aspirin should not be routinely administered.

Optimal oral anticoagulant therapy in Chinese patients with mechanical heart valves.

BACKGROUND: The oral administration of anticoagulants is an effective means of preventing thromboembolic complications in patients implanted with mechanical valves. This treatment strategy, however, entails a dose-dependent in the risk of hemorrhage that is a cause for concern in China. As such, in this study, we sought to better determine what the ideal oral anticoagulant therapy intensity is in a Chinese population of patients implanted with mechanical valves. METHODS: In the present observational cohort study, we observed the outcomes of eligible enrolled patients that had been implanted with St. Jude Medical prosthetic valves and who had been treated at our institution from 2013 onwards. All enrolled patients were followed for between 1 and 6 years through outpatient visits or telephone interviews following discharge. Study endpoints included instances of thromboembolism and major hemorrhage. We calculated the international normalized ratio (INR)-specific incidence of such adverse events as a means of determining optimal anticoagulant therapeutic intensity in patients with these bileaflet mechanical valve prostheses. RESULTS: In total this study enrolled 3176 patients, of whom 3017 were followed for 12,746.08 total person-years (4.22 mean years per patient), while the remaining 159 patients (5%) were lost during follow-up. A total of 182 patients suffered from adverse events, with a roughly 1.43% annual incidence rate of such adverse events (95% confidence interval [CI], 1.22-1.64). Of these, 54 patients suffered from episodes of major bleeding (0.42% per patient-year, 95% CI, 0.31-0.53), while 131 suffered from thromboembolism (1.03% per patient-year, 95% CI, 0.85-1.21). Based on these analyses, we determined that the ideal low-intensity anticoagulant treatment regimen for patients with bileaflet mechanical heart valve prostheses was an INR between 1.5 and 2.5. In those patients that had undergone aortic valve replacement (AVR), the optimal INR was between 1.5 and 2.0 regardless of any thromboembolism risk factors in these patients. In contrast, in patients that had undergone mitral valve replacement (MVR) who were not at risk for thromboembolism, the optimal INR was between 1.5 and 2.0, whereas in those at risk of thromboembolism the optimal INR was between 2.0 and 2.5. The ideal anticoagulant intensity in patients undergoing both AVR and MVR (DVR) was the same as in patients undergoing MVR alone. CONCLUSIONS: In order to achieve optimal outcomes by maintaining effective anticoagulant dosing while entailing minimal risk in Chinese patients that have undergone a bileaflet mechanical valve replacement, the target INR range should be between 1.5 and 2.5, with the final intensity of this anticoagulant regimen being determined based on a given patient's risk of thromboembolism.