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Genotype-guided Warfarin Dosing in Patients with Mechanical Valves: a Randomized Controlled Trial.
Ann Thorac Surg. 2018 Sep 08;:
Authors: Xu Z, Zhang SY, Huang M, Hu R, Li JL, Cen HJ, Wang ZP, Ou JS, Yin SL, Xu YQ, Wu ZK, Zhang X
Abstract
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 and one patients were randomized, 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%-99.2%). Compared with the control group, the study group shortened the time to reach a stable dose (mean: 42.09±23.655d versus 33.52±20.044d, 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 had higher International Normalized Ratio (INR) variability than patients with the CYP2C9 *1/*1 (P=0.024). Compared with normal and sensitive responders, the highly sensitive ones were at increased risk of an INR≥4.0 (P<0.05).
CONCLUSIONS: The genotype-guided warfarin dosing was safe and might be more efficient with respect to the time to reach a stable dose. Pharmacogenomic testing might be beneficial to identify the patients with the CYP2C9 *1/*3 and the highly sensitive responders, who were high risk subgroup of patients with mechanical heart valves.An appropriately powered study is needed to further confirm the above findings.
PMID: 30205115 [PubMed - as supplied by publisher]