Preliminary Study on the Relationship between VKORC1 Gene Polymorphism and Warfarin Anticoagulant Therapy in Chinese patients with Continuous-Flow Left Ventricular Assist Devices

Abstract

Abstract 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.