ESTIMATION OF THE WARFARIN DOSE IN HEART FAILURE PATIENTS WITH IMPLANTED MECHANICAL CIRCULATORY SUPPORT DEVICE

Abstract

Relevance. Left ventricular assist device (LVAD) is an alternative treatment for heart failure (HF) patients which
improves patient’s quality of life at their end-stage. Despite to the improvement LVAD is beleaguered with
thrombosis/bleeding complications in 70% of HF patients after implantation. An anticoagulant treatment of warfarin is usually
prescribed to reduce thrombosis complications. However, due to the incorrect dosage of the treatment thrombosis/ bleeding
complications still happen. Warfarin dose could be identified by genetic variants of vitamin K-epoxide reductase complex
(VKORC1) and the cytochrome P450-2C9 (CYP2C9) which account for 50% of dose variability.
Aim. The aim of our investigation is to identify variability of warfarin dose according to the genotype polymorphisms of
genes and their difference from the clinical dosage in HF patients.
Materials and methods. The case series study included 98 HF patients (without complications – 74 patients, with
complications – 24 patients) with prescribed warfarin treatment after device implantation. Clinical warfarin dosage difference
was identified between genotype polymorphisms of rs9923231, rs9934438 in VKORC1 gene. Furthermore, warfarin dosage
was calculated according to the genetic test results and compared with clinical dosage.
Results. Warfarin dosage according to the clinical protocol between three genotypes of polymorphisms in VKORC1
gene showed significant difference. HF patients were prescribed with higher warfarin dosage with wild type genotype
polymorphism of rs9934438 in VKORC1 gene than with mutant genotype < 2.5mg (3.88 ± 1.25 vs. 2.44 ± 0.81, p =
0.00005).
Conclusion. Genotype-guided warfarin dosing may estimate accurate dose and potentially improve outcomes in LVAD
patients.