Key result
Genetic testing to guide initial warfarin dosing after aortic valve replacement significantly increased the percentage of patients achieving target INR on the sixth postoperative day (73.3% vs 58.3%) compared to standard dosing.
Why the study?
The study was conducted to explore the role of VKORC1 and CYP2C9 genetic testing in determining warfarin dosage after aortic valve replacement.
Does genetic testing-guided warfarin dosing improve the achievement of target INR and reduce critical INR values in patients after aortic valve replacement?
Cohort (n=172)
Open-label
No
Does genetic testing-guided warfarin dosing improve the achievement of target INR and reduce critical INR values in patients after aortic valve replacement?
Absolute Event Rate: 73.3% vs 58.3%
p-value: p=<0.05
Genotype-guided warfarin dosing after mechanical aortic valve replacement significantly increases the proportion of patients achieving target INR early postoperatively and reduces the incidence of critical INR values compared to standard dosing.
May support genotype-guided warfarin dosing post-AVR; leaves open outcome benefits in randomized trials.
OBJECTIVE: To explore the role of genetic testing of VKORC1 and CYP2C9 in determining the dosage of warfarin after aortic valve replacement. METHODS: A total of 172 patients receiving warfarin after aortic valve replacement were divided into a control group (n = 86) and an experimental (n = 86) group based on acceptance of genetic testing. In the experimental group, three loci of VKORC1 and CYP2C9 were tested by polymerase chain reaction-restriction fragment length polymorphism technique, and the initial dose of warfarin was determined based on the genetic testing results and warfarin oral-dose table recommended by U.S. Food and Drug Administration (FDA). In the control group, warfarin (3 mg per night) was used as the initial dose. The international normalized ratio (INR) of each patient was continuously monitored after medication. The percentages of patients meeting the target INR in the two groups at specific time points and at 3-month follow-up after discharge from the hospital were monitored, and the incidence of various adverse events was compared between the groups. RESULTS: Based on the results of genetic testing, 68 patients received 3-4 mg/d (79.1%), 10 patients received 0.5-2 mg/d (11.6%), and eight patients received 5-7 mg/d (9.3%) as the initial dosages of warfarin in the experimental group. The percentages of the patients meeting the target INR on the third and sixth day of postoperative medication were 45.3% and 73.3%, respectively, in the experimental group, and 29.8% and 58.3%, respectively, in the control group. The INR critical values during hospitalization occurred in 2.3% in the experimental group and in 7.1% in the control group, while the percentage of the patients meeting the target INR after 3 months was 86.1% in the experimental group and 83.1% in the control group. CONCLUSION: Genetic testing may guide the selection of the initial dose of warfarin after heart valve replacement to rapidly achieve a stable dose.
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Zhang et al. (2022) conducted a cohort in Mechanical aortic valve replacement requiring warfarin therapy (n=172). Genetic testing of VKORC1 and CYP2C9 to guide warfarin dosing vs. Standard initial dose of warfarin (3 mg/d) was evaluated on Percentage of patients meeting the target INR on the sixth day of postoperative medication (p=<0.05). Genetic testing to guide initial warfarin dosing after aortic valve replacement significantly increased the percentage of patients achieving target INR on the sixth postoperative day (73.3% vs 58.3%) compared to standard dosing.
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