Key result
Patients with the VKORC1 -1639AA genotype reached the target INR significantly faster than those with the GA genotype (5.6 vs. 14.6 days) and required a lower cumulative warfarin dose.
Why the study?
This study explored the effect of VKORC1 gene polymorphism on early warfarin dosage and time in therapeutic range within 3 months of LVAD implantation to inform anticoagulation decision-making.
Does the VKORC1 -1639AA genotype reduce the time to target INR and warfarin dose requirements compared to the GA genotype in Chinese patients with CF-LVADs?
Observational (n=20)
No
Does the VKORC1 -1639AA genotype reduce the time to target INR and warfarin dose requirements compared to the GA genotype in Chinese patients with CF-LVADs?
Absolute Event Rate: 5.6% vs 14.6%
p-value: p=<0.001
In Chinese patients with CF-LVADs, the VKORC1 -1639AA genotype is associated with a faster time to target INR and lower warfarin dose requirements compared to the GA genotype, though it does not affect medium-term time in therapeutic range.
VKORC1 -1639AA genotype was associated with faster target INR and lower warfarin dose in Chinese CF-LVAD patients; hypothesis-generating and should not yet change practice.
Purpose This study explored the effect of VKORC1 gene polymorphism on the early application of warfarin dosage in left ventricular assist device (LVAD) implantation as well as the time in therapeutic range (TTR) within 3 months of surgery, thereby providing a basis for anticoagulation decision-making in patients with LVADs. Methods Retrospective analysis was used to review the warfarin-related genetic data of patients who underwent LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to August 2021. This study analyzed the effects of different genotypes on (1) the number of days to reach the target international normalized ratio (INR) (defined as 2.0–2.5); (2) the cumulative dose, average dose, and last dose before reaching the target INR; and (3) the TTR within 3 months of LVAD implantation. Results Out of 20 patients, 15 patients (75.0%) had VKORC1 − 1639AA and CYP2C9*1/*1 polymorphisms, and 5 patients (25.0%) had VKORC1 − 1639GA and CYP2C9*1/*1 polymorphisms. Compared with patients with LVADs carrying the VKORC1 − 1639GA genotype, those carrying the VKORC1 − 1639AA genotype took significantly fewer days to reach the target INR (5.6 vs. 14.6 days, P < 0.001), a lower cumulative warfarin dose (20.5 vs. 66.2 mg, P < 0.001), a lower average warfarin dose (3.5 vs. 4.5 mg, P = 0.030), and a lower dose of the final warfarin administered before the target INR was achieved (3.4 vs. 5.5 mg, P = 0.030). The percentage of TTR was not significantly different between the two VKORC1 genotypes on days 7–30 (50.00% for the AA genotype vs. 45.29% for the GA genotype, P = 0.26) or days 31–90 (53.03% for the AA genotype vs. 50.93% for the GA genotype, P = 0.25) after LVAD implantation. Conclusion Patients with the VKORC1 − 1639AA genotype reached the target INR faster than those with the GA genotype, and the total dose needed to achieve the target was smaller. Genotype-guided warfarin dosing may allow safer anticoagulation by achieving the target INR with less risk to the patient, but it did not affect long-term TTR management in this study.
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Yu et al. (2022) conducted an observational in Continuous-flow left ventricular assist device (CF-LVAD) implantation requiring warfarin (n=20). VKORC1 -1639AA genotype vs. VKORC1 -1639GA genotype was evaluated on Days to reach target INR (2.0-2.5) (p=<0.001). Patients with the VKORC1 -1639AA genotype reached the target INR significantly faster than those with the GA genotype (5.6 vs. 14.6 days) and required a lower cumulative warfarin dose.
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