The Role of Clinical Variables and VKORC1 Polymorphism in Efficacy and Stability of Acenocoumarol in Neurological Patients

J Neurosci Rural Pract. 2018 Apr-Jun;9(2):186-192. doi: 10.4103/jnrp.jnrp_306_17.

Abstract

Objective: To analyze the clinical importance of VKORC1 polymorphism and its correlation with stability of oral anticoagulation.

Patients and methods: In a hospital-based study, the patients on oral anticoagulant (OAC) were included during 2013-2016. The patients received OAC for cardioembolic stroke, cerebral venous sinus thrombosis (CVST), and prevention of deep vein thrombosis (DVT). Demographic, clinical, and neurological findings were recorded. Stability of anticoagulation was determined by percentage of time international normalized ratio (INR) values were in therapeutic range. Time in therapeutic range (TTR) >65% was defined as stable and <65% was defined unstable. VKORC 1 polymorphism was studied by polymerase chain reaction and correlated with daily dose of OAC and stability of INR.

Results: A total of 157 patients with a median age of 40 years were included in the study. Ninety-two patients received OAC for secondary stroke prevention, 62 for CVST, and 3 for DVT. Out of 2976 INR reports, 1458 (49%) were in the therapeutic range, 997 (33.1%) were below the therapeutic range, and 521 (17.5%) were above the therapeutic level. Stable INR was obtained in 75 (47.77%) patients which was improved by drug modification in 3 and dietary adjustment in 12 patients. VKORC1 polymorphism revealed GG genotype in 127 (80.9%), GA genotype in 22 (14%), and AA genotype in 8 (5.1%) patients. Therapeutic range of INR was seen in 49%, below therapeutic range was seen in 31.5%, and above in 17.5%.

Conclusion: VKORC1 polymorphism was related to mean daily dose of OAC but not to the stability of INR.

Keywords: Cardioembolic stroke; VKORC1 gene polymorphism; Vitamin K antagonist; international normalized ratio stability; oral anticoagulation.