Abstract TP406: Impact Of Warfarin Pharmacogenomics In The Time In Therapeutic Range In Korean Patients With Atrial Fibrillation.

Abstract

Background: Warfain is highly effective for stroke prevention in patients with atrial fibrillation (AF), but also has narrow therapeutic window (usually INR 2-3). Even in clinical trials with selected, closely monitored patients, the times in therapeutic range (TTR) of those taking warfarin is less than two thirds. Single nucleotide polymorphisms in genes affecting warfarin metabolism (cytochrome-P450 2C9, CYP2C9) and response (vitamin-K epoxide reductase complex 1, VKORC1) have an important influence on warfarin therapy. Initial INR response to warfain was reportedly associated with genetic variability in VKORC1 than with CYP2C9. However, warfarin pharmacogenics associated with long-term intraindividual variation (TTR during the warfarin maintenance) is unsettled. Methods: Clinical and genetic data form 330 Korean patients with AF (200 had AF-related stroke) were collected and followed for average 36 months. Patients were included who had AF, who were eligible to take warfarin , in whom genetic testing was available, and who were followed for more than 6 months. Thromboembolism and hemorrhagic complication was monitored with clinical and laboratory findings, including thromboemoblic [CHADS2 and CHA2DS2-Vasc] and hemorrhagic [ATRIA] risk schemes, as confounders. Results: Genotypic frequencies of CYP2C9 *1/*1, *1/*3, and *3/*3 were 90%, 6.7%, 0.3%, respectively, whereas VKORC1 +1173 TT, CT, and CC were 84%, 15.2%, 0.6%, respectively. TTR varies greatly depending on the CYP2C9 polymorphism: TTR of INR 2-3 was 65±20% in *1/*1 carriers, 42±22% in *1/*3 carriers, and 1.4±2.2% in *3/*3 carriers. TTR of INR was not different depending on the VKORC1 polymorphism. Conclusions: Novel oral anticoagulants have recently been introduced. However, there is a lack of consensus regarding the indication of these novel agents in patients with AF. Our results indicated that TTR during warfarin maintenance was associated with genetic variability in CYP2C9 than with VKORC1. Warfarin alternatives could be particularly helpful in patients who have specific CYP2C9 polymorphism other than *1/*1. Further studies are needed testing the impact of warfarin genetic polymorphism in other ethnic group (i.e. white) where these CYP2C9 polymorphisms were prevalent.