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

Veli K Topkara1, Robert J Knotts, Douglas L Jennings

  • 1From the *Division of Cardiology, Department of Medicine, †Department of Pharmacy, ‡Division of Cardiothoracic Surgery, Department of Surgery, Columbia University Medical Center, New York Presbyterian, New York, New York; §Division of Cardiology, Department of Medicine, University of Chicago, Chicago, Illinois; ¶Division of Hematology, Department of Medicine, Columbia University Medical Center, New York Presbyterian, New York, New York; and ‖Division of Cardiology, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York.

ASAIO Journal (American Society for Artificial Internal Organs : 1992)
|June 4, 2016
PubMed

Insights

Warfarin dosing for continuous-flow left ventricular assist device (CF-LVAD) patients can be improved using genetic testing. VKORC1 gene variants significantly impact warfarin dose and time to reach target INR, suggesting personalized anticoagulation strategies.

Area of Science:

  • Cardiology
  • Pharmacogenomics
  • Medical Devices

Background:

  • Continuous-flow left ventricular assist device (CF-LVAD) therapy is crucial for end-stage heart failure but is complicated by bleeding and thrombotic events.
  • Warfarin dosing is complex, and while FDA recommends considering genetic information, its utility in CF-LVAD patients remains understudied.

Purpose of the Study:

  • To investigate the clinical utility of warfarin pharmacogenetic testing (CYP2C9 and VKORC1) for optimizing anticoagulation in CF-LVAD patients.
  • To determine the association between specific gene variants and warfarin dosing parameters, including time to target international normalized ratio (INR) and total/maintenance doses.

Main Methods:

  • Genotype testing for CYP2C9 (*1, *2, *3) and VKORC1 (-1639 G>A) polymorphisms was performed in 90 CF-LVAD patients.
  • Outcomes analyzed included time-to-target INR, total warfarin dose, and maintenance warfarin dose in relation to patient genotypes.

Main Results:

  • CF-LVAD patients with a rare VKORC1 gene variant required significantly lower cumulative warfarin doses (18.9 vs. 35.0 mg, p=0.002) to achieve target INR.
  • These patients also spent fewer days reaching target INR (4.9 vs. 7.0 days, p=0.021) and required lower discharge warfarin doses (3.2 vs. 5.6 mg, p=0.001) compared to those with wild-type genotypes.

Conclusions:

  • VKORC1 genotype significantly influences warfarin requirements and anticoagulation time in CF-LVAD patients.
  • Genotype-guided warfarin dosing holds potential for improving anticoagulation safety and patient outcomes in this population.

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