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. 2018 Jul;74(7):885-894.
doi: 10.1007/s00228-018-2483-8. Epub 2018 May 21.

Effects of vitamin K epoxide reductase complex 1 gene polymorphisms on warfarin control in Japanese patients with left ventricular assist devices (LVAD)

Kazuki Nakagita  1   2 , Kyoichi Wada  1 , Yutaro Mukai  1   2 , Takaya Uno  1   2 , Ryoji Nishino  1 , Sachi Matsuda  1 , Hiromi Takenaka  1 , Nobue Terakawa  1 , Akira Oita  1 , Mitsutaka Takada  3
Affiliations

Effects of vitamin K epoxide reductase complex 1 gene polymorphisms on warfarin control in Japanese patients with left ventricular assist devices (LVAD)

Kazuki Nakagita et al. Eur J Clin Pharmacol. 2018 Jul.

Abstract

Purpose: This study aimed to investigate relationships between times in therapeutic range (TTR) or warfarin sensitivity indexes (WSI) and VKORC1-1639G>A and CYP2C9 polymorphisms in patients with left ventricular assist devices (LVAD).

Methods: Severe heart failure patients who received LVAD from January 1, 2013 to October 31, 2017 were recruited. Relationships between TTR or WSI and VKORC1-1639G>A and CYP2C9 gene polymorphisms were investigated immediately after LVAD implantation (period 1) and immediately prior to hospital discharge (period 2).

Results: Among 54 patients, 31 (72.1%) had VKORC1-1639AA and CYP2C9*1/*1 (AA group) polymorphisms and 12 (27.9%) had VKORC1-1639GA and CYP2C9*1/*1 (GA group) polymorphisms. During period 1, mean prothrombin time-international normalized ratio (PT-INR) values were significantly higher in the AA group than in the GA group (2.21 vs. 2.05, p < 0.0001). Mean WSI values were 1.68-fold greater in the AA group than in the GA group (1.14 vs. 0.68, p < 0.0001). In addition, times below the therapeutic range (TBTR) in the GA group were significantly greater than in the AA group during period 1 (39.8 vs. 28.3%, p = 0.032), and insufficient PT-INR was more frequent in the GA group than in the AA group. However, mean PT-INR values during period 2 did not differ and no significant differences in TTR, TATR, and TBTR values were identified. In subsequent multivariable logistic regression analyses, the VKORC1-1639GA allele was significantly associated with insufficient anticoagulation.

Conclusion: Patients with the VKORC1-1639GA and CYP2C9*1/*1 alleles may receive insufficient anticoagulation therapy during the early stages after implantation of LVAD, and VKORC1-1639G>A and CYP2C9 genotyping may contribute to more appropriate anticoagulant therapy after implantation of LVAD.

Keywords: CYP2C9; Left ventricular assist device; Time in therapeutic range; VKORC1-1639G>A; Warfarin; Warfarin sensitivity index.

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