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

Veli K. Topkara, Robert J. Knotts, Douglas L. Jennings, A. Reshad Garan, Allison P. Levin, Alexander Breskin, Francesco Castagna, Barbara Cagliostro, Melana Yuzefpolskaya, Koji Takeda, Hiroo Takayama, Nir Uriel, Donna M. Mancini, Andrew Eisenberger, Yoshifumi Naka, Paolo C. Colombo, Ulrich P. Jorde

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)558-564
Number of pages7
JournalASAIO Journal
Volume62
Issue number5
DOIs
StatePublished - Sep 1 2016

Keywords

  • left ventricular assist device
  • pharmacogenomics
  • thrombosis
  • warfarin

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

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  • Cite this

    Topkara, V. K., Knotts, R. J., Jennings, D. L., Garan, A. R., Levin, A. P., Breskin, A., Castagna, F., Cagliostro, B., Yuzefpolskaya, M., Takeda, K., Takayama, H., Uriel, N., Mancini, D. M., Eisenberger, A., Naka, Y., Colombo, P. C., & Jorde, U. P. (2016). Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices. ASAIO Journal, 62(5), 558-564. https://doi.org/10.1097/MAT.0000000000000390