Quality Control And Management Of The Clinical Application Of Warfarin

Warfarin is the most widely used first-line anticoagulant. Despite its effectiveness, ithas long been listed among the top ten drugs causing adverse events by FDA due to itsnarrow therapeutic range, large variations in individual dosing and significant druginteractions. So it is necessary to conduct quality control and management on itsclinical application of anticoagulant therapy.The results of meta-analysis indicated that TTR which was selected as the qualitycontrol index had negative correlations with hemorrhagic and thrombotic adverseevents. Anticoagulantion clinic, patient self-monitor/management and dosing modelcould improve the value of TTR. And dosing model was the most focused researchtopic of this study.Deriving from the warfarin-Dantonic drug-drug interaction clinical trial, a warfarindosing model based on early INR response and subsequent dose was established andeven more accurate than pharmacogenetic model through predicted performancecomparison. The established INR dosing model could explain86.8%of variations inindividual dosing, and the proportion of subjects whose predicted doses were within20%of their actual therapeutic doses was66.7%. Thus, early INR could provideinformation about warfarin sensitivity additional to that provided by genepolymorphism and improve the prediction accuracy of dosing model.Decision tree and Markov models were combined to conduct cost-effectivenessanalysis of INR and pharmacogenetic dosing models for the evidence-based decisionmaking. It indicated that pharmacogenetic dosing model was cost-effect if TTR wasimproved by14.5%, the proportion of INR above the therapeutic range was below10.4%or the costs for the measurements of CYP2C9and VKORC1were below187.5USD/time. However, the established INR dosing model was cost-effect if TTR couldbe improved comparing with the usual care. INR dosing model could increase theQALY and reduce the costs of anticoagulant therapy simultaneously. And it showedsignificant advantage in the cost-effectiveness perceptive comparing with thepharmacogenetic dosing model.Strategies for the quality control and management on warfarin anticoagulant therapyarisen from this study, especially the established INR dosing model could improve theeffectiveness, safety of anticoagulant therapy and its benefit to society. Results of this study provided the evidence for the warfarin clinical application evidence-baseddecision making.