Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices

ASAIO J. 2016 Sep-Oct;62(5):558-64. doi: 10.1097/MAT.0000000000000390.

Abstract

Bleeding and thrombotic complications continue to plague continuous-flow left ventricular assist device (CF-LVAD) therapy in patients with end-stage heart failure. Warfarin genotyping information can be incorporated into decision making for initial dosing as recommended by the Food and Drug Administration; however, clinical utility of this data in the CF-LVAD population has not been well studied. Genotypes testing for CYP2C9 and VCORC1 polymorphisms were determined in 90 CF-LVAD patients. Outcomes studied were the association of CYP2C9 (*1, *2, or *3) and VKORC1 (-1639 G>A) gene variants with time-to-target international normalized ratio (INR), total warfarin dose, maintenance warfarin dose. Continuous-flow left ventricular assist device patients carrying a rare variant in the VKORC1 gene had a significantly lower cumulative warfarin dose until target INR achieved (18.9 vs. 35.0 mg, p = 0.002), days spent until INR target achieved (4.9 vs. 7.0 days, p = 0.021), and discharge warfarin dose (3.2 vs. 5.6 mg, p = 0.001) compared with patients with wild-type genotype. Genotype-guided warfarin dosing may lead to safer anticoagulation and potentially improve outcomes in CF-LVAD patients.

MeSH terms

  • Anticoagulants / administration & dosage*
  • Blood Coagulation / drug effects
  • Blood Coagulation / genetics
  • Cytochrome P-450 CYP2C9 / genetics*
  • Female
  • Genotype
  • Heart-Assist Devices / adverse effects*
  • Hemorrhage / etiology
  • Hemorrhage / genetics
  • Humans
  • International Normalized Ratio
  • Male
  • Polymorphism, Genetic
  • Vitamin K Epoxide Reductases / genetics*
  • Warfarin / administration & dosage*

Substances

  • Anticoagulants
  • Warfarin
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases