Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices.
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.
From 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.
Veli K
VK
Topkara
Robert J
RJ
Knotts
Douglas L
DL
Jennings
A Reshad
AR
Garan
Allison P
AP
Levin
Alexander
A
Breskin
Francesco
F
Castagna
Barbara
B
Cagliostro
Melana
M
Yuzefpolskaya
Koji
K
Takeda
Hiroo
H
Takayama
Nir
N
Uriel
Donna M
DM
Mancini
Andrew
A
Eisenberger
Yoshifumi
Y
Naka
Paolo C
PC
Colombo
Ulrich P
UP
Jorde
D000925:Anticoagulants / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006470:Hemorrhage / Q000209:etiology / Q000235:genetics; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases