Frequent point of care monitoring demonstrates the safety of low intensity warfarin therapy in Asian patients with mechanical heart valve

Abstract

Genetic variants of the main cytochrome P-450 (CYP) and ethnicity may influence warfarin dosing. Chinese patients are reportedly more sensitive than Caucasians to the anticoagulant effect of warfarin. The use of the Point of Care Testing (POCT) and frequent monitoring of the international normalization ratio (INR) had facilitated measurements of essential coagulation parameters of warfarin therapy. To our knowledge, POCT has not been evaluated in clinical trials that underlay ethnic differences between different geographic regions. We have conducted a multi-center prospective trial to evaluate the safety of low warfarin dose, and the role of frequent INR measurements by POCT in Chinese patients. A total of 488 patients from 11 geographically diverse hospitals in China underwent implantation with CarboMedics aortic or mitral valve prosthesis (Sulzer Medica, Austin, TX). Patients received two consecutive doses of 2.5 mg warfarin at 24 and 72 h post-surgery, followed by a daily dose to maintain INR range of 1.5–2.5. The follow-up was performed weekly or biweekly and the INR was measured on fingerstick fresh whole blood, using the HEMOCHRON Signature Microcoagulation system (ITC, NJ). The majority (99.3%) of Chinese patients who required prosthetic heart valve and warfarin therapy were \70 years old with a mean age of 45.28 ± 12. The mean follow-up duration was 86.8 ± 11.2 weeks (range 72–104 weeks). A total of 4,886 INR values were obtained with a mean INR in all 11 sites at 1.76 ± 0.50. The majority of INR values (67.8%, n = 3,312), was in therapeutic range (1.5–2.5), a moderate number was below range (26.2%, n = 1,281), whereas only 6.0% (n = 293) of INR value was above range. Mean daily maintenance dose was 2.5 ± 0.60 mg in all sites; a significant reduction from age-matched ACCP guideline for rest of the world (ROW) patients. Minor bleeding occurred in 42 cases, no patient required hospitalization. Major adverse events (4 cases) were lower than reported ROW data. The maintenance of antithrombotic efficacy with low warfarin requirement and narrow INR range in Chinese patients was independent of demographic factors and geographic locations. Frequent INR-POCT confirmed the safety of low dose warfarin requirements in Chinese patients. Monitoring by POCT may provide a mean to standardize warfarin monitoring across diverse geographic regions and therefore allow the analysis of ethnic variation in various subpopulations.