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

Veli K. Topkara, Robert J. Knotts, Douglas L. Jennings, A. R. 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

3 Citations (Scopus)

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 FDA; 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 INR, total warfarin dose, maintenance warfarin dose. CF-LVAD 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 to 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)
JournalASAIO Journal
DOIs
StateAccepted/In press - Jun 1 2016

Fingerprint

Left ventricular assist devices
Heart-Assist Devices
Warfarin
Genes
International Normalized Ratio
Genotype
Polymorphism
Plague
Decision making
Cytochrome P-450 CYP2C9
Decision Making
Heart Failure
Maintenance
Hemorrhage
Testing
Population

ASJC Scopus subject areas

  • Biophysics
  • Biomaterials
  • Bioengineering
  • Biomedical Engineering
  • Medicine(all)

Cite this

Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices (CF-LVADs). / Topkara, Veli K.; Knotts, Robert J.; Jennings, Douglas L.; Garan, A. R.; Levin, Allison P.; Breskin, Alexander; Castagna, Francesco; Cagliostro, Barbara; Yuzefpolskaya, Melana; Takeda, Koji; Takayama, Hiroo; Uriel, Nir; Mancini, Donna M.; Eisenberger, Andrew; Naka, Yoshifumi; Colombo, Paolo C.; Jorde, Ulrich P.

In: ASAIO Journal, 01.06.2016.

Research output: Contribution to journalArticle

Topkara, VK, Knotts, RJ, Jennings, DL, Garan, AR, Levin, AP, Breskin, A, Castagna, F, Cagliostro, B, Yuzefpolskaya, M, Takeda, K, Takayama, H, Uriel, N, Mancini, DM, Eisenberger, A, Naka, Y, Colombo, PC & Jorde, UP 2016, 'Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices (CF-LVADs)', ASAIO Journal. https://doi.org/10.1097/MAT.0000000000000390
Topkara, Veli K. ; Knotts, Robert J. ; Jennings, Douglas L. ; Garan, A. R. ; Levin, Allison P. ; Breskin, Alexander ; Castagna, Francesco ; Cagliostro, Barbara ; Yuzefpolskaya, Melana ; Takeda, Koji ; Takayama, Hiroo ; Uriel, Nir ; Mancini, Donna M. ; Eisenberger, Andrew ; Naka, Yoshifumi ; Colombo, Paolo C. ; Jorde, Ulrich P. / Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices (CF-LVADs). In: ASAIO Journal. 2016.
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