Genotype-guided Warfarin Dosing in Patients with Mechanical Valves: a Randomized Controlled Trial.

Background. The clinical utility of genotype-guided warfarin dosing remains controversial. The objective of this trial was to evaluate the efficacy and safety of genotype-guided warfarin dosing in East Asians. Methods. A double-blind, randomized control trial was performed to compare a genotype-guided dosing algorithm (CYP2C9, VKORC1, and CYP4F2) with a clinical-guided one in the initiation treatment for patients with mechanical heart valves. The primary outcomes included the time to reach a stable dose and the percentage of time in the therapeutic range (TTR). Results. Two hundred one patients were randomly assigned to treatment, 101 to control and 100 to study. The major bleeding and thromboembolic event-free rate in the study group was 97.0% (95% confidence interval: 90.9% to 99.2%). Compared with the control group, the study group shortened the time to reach a stable dose (mean: 42.09 +/- 23.655 days versus 33.52 +/- 20.044 days p = 0.009). The TTRs were 47.257% and 47.461% in the control and study group (p = 0.941), respectively. Patients with the CYP2C9 *1/*3 genotype had higher international normalized ratio (INR) variability than patients with the CYP2C9 *1/*1 genotype (p = 0.024). Compared with normal and sensitive responders, the highly sensitive responders were at increased risk of an INR of 4.0 or greater (p < 0.05). Conclusions. The genotype-guided warfarin dosing was safe and might be more efficient for the time to reach a stable dose. Pharmacogenomic testing might be beneficial to identify the patients with the CYP2C9 *1/*3 genotype and the highly sensitive responders, who were in the high-risk subgroup of patients with mechanical heart valves. An appropriately powered study is needed to further confirm these findings. (C) 2018 by The Society of Thoracic Surgeons