Does Computer Simulation Help Facilitate Personalized Precision Medicine for the Use of Warfarin?

Abstract

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 …