Abstract 2336: Requiring Lower Warfarin Dosages to Achieve Therapeutic Anticoagulation is a Strong Risk Factor for Bleeding Event
BACKGROUND Despite its complex pharmacokinetic and pharmacodynamic profile, warfarin is still one of the most widely used. Accumulating evidence suggests some genotypes of enzymes are associated with low maintenance dose requirement and increased risk of major bleeding. However, unpredictable dose-response variations of warfarin are markedly influenced by pharmacokinetic and pharmacodynamic aspects that are determined not only by genetic but also by many other factors. METHODS In a prospective cohort from 550 consecutive patients with mechanical valve replacement were studied. We evaluated the incidence of bleeding according to maintenance warfarin dosages to achieve therapeutic anticoagulation. Patients were divided into three groups (lower dosage group, warfarin maintenance dose 0.2mg/day/ BMI).
RESULTS Over 4000 patient-years of follow-up, PT-INR values fell within target range for 90.2% of the time on treatment. Association between bleeding event and each risk factor including levels of INR were combined and simultaneously computed in Cox hazard model with multivariate analysis. There was no difference between three groups about patient characteristics including anticoagulant intensity. However, low dosage group have significantly increased risk of bleeding (figure⇓).
CONCLUSION Requiring lower warfarin dosages to achieve therapeutic anticoagulation is a strong risk factor for bleeding event. The pharmacogenetics-oriented management of warfarin therapy is not needed. To evaluate maintenance dose of warfarin is easy and cost-effectivance, but very useful to manage anticoagulant therapy safely.