Does Computer Simulation Help Facilitate Personalized Precision Medicine for the Use of Warfarin?
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In this issue of Circulation: Cardiovascular Genetics, Ravvaz et al1 presented an interesting report on the evaluation of warfarin dosing protocols among patients with atrial fibrillation with various different clinical backgrounds. This article is unique in reporting a new method using a computer simulation–based approach.
See Article by Ravvaz et al
To date, anticoagulation effects of warfarin are monitored by prothrombin time international normalized ratio (PT-INR).2 The appropriate warfarin dose to achieve the target PT-INR is affected by various factors, including age, sex, comorbidity, concomitant drug,3 and genetic polymorphisms of specific enzymes related to warfarin metabolism, such as vitamin K epoxide reductase complex and CYP2C9.4 After clarification of warfarin metabolism, the impact of genetics on the PT-INR control with warfarin was of particular interest. Conflicting results have been published to date on the improvement of PT-INR control using genotype-guided warfarin dosing.5–8 Despite speculated impacts of the 2 enzymes directly related to warfarin metabolism, prediction of appropriate warfarin dose in individual patients using genotype information had less impact than expected. Furthermore, the impact of genotype-guided warfarin dose adjustment strategy on the clinical outcome rather than achieving target PT-INR is difficult to prove because clinical outcomes are influenced by multiple factors including those that could not be monitored by PT-INR control. Randomized clinical trials give us strong scientific evidences but require substantial numbers of real patients who agree to participate into the trials. Constructive …