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

doi:10.1097/MAT.0000000000000390

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

Medicine

Research output: Contribution to journal › Article › peer-review

14 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 language	English (US)
Pages (from-to)	558-564
Number of pages	7
Journal	ASAIO Journal
Volume	62
Issue number	5
DOIs	https://doi.org/10.1097/MAT.0000000000000390
State	Published - Sep 1 2016

Keywords

left ventricular assist device
pharmacogenomics
thrombosis
warfarin

ASJC Scopus subject areas

Biophysics
Bioengineering
Biomaterials
Biomedical Engineering

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10.1097/MAT.0000000000000390

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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

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', ASAIO Journal, vol. 62, no. 5, pp. 558-564. https://doi.org/10.1097/MAT.0000000000000390

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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.",

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AU - Knotts, Robert J.

AU - Jennings, Douglas L.

AU - Garan, A. Reshad

AU - Levin, Allison P.

AU - Breskin, Alexander

AU - Castagna, Francesco

AU - Cagliostro, Barbara

AU - Yuzefpolskaya, Melana

AU - Takeda, Koji

AU - Takayama, Hiroo

AU - Uriel, Nir

AU - Mancini, Donna M.

AU - Eisenberger, Andrew

AU - Naka, Yoshifumi

AU - Colombo, Paolo C.

AU - Jorde, Ulrich P.

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N2 - 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.

AB - 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.

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

Abstract

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ASJC Scopus subject areas

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