Genotype-Guided Warfarin Dosing in Patients With Mechanical Valves: A Randomized Controlled Trial.
Ann Thorac Surg
; 106(6): 1774-1781, 2018 12.
Article
in En
| MEDLINE
| ID: mdl-30205115
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 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Warfarin
/
Heart Valve Prosthesis
/
Anticoagulants
Type of study:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Ann Thorac Surg
Year:
2018
Document type:
Article
Affiliation country:
China