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- Title
Stability of Anticoagulation Following Acenocoumarin in Stroke Patients: Role of Pharmacogenomics and Acquired Factors.
- Authors
Dubey, Ashish Kant; Kalita, Jayantee; Nizami, Mohammad Firoz; Kumar, Surendra; Misra, Usha Kant
- Abstract
Objective: Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and cerebral venous sinus thrombosis (CVST). We report the role of cytochrome P450 (CYP2C9*2/*3) and vitamin K epoxide reductase subunit 1 (VKORC1) genotypes and acquired causes in maintaining stability of anticoagulation following acenocoumarin in cardioembolic stroke and CVST. Methods: The study comprised 157 individuals with cardioembolic stroke and CVST who were on acenocoumarin. Their comorbidities, comedication, and dietary habits were noted. Prothrombin time and international normalized ratio (INR) were measured during follow-up, and the coagulation status was categorized as stable (>50% occasions in therapeutic range) and unstable (>50% below and above therapeutic range). Genotyping of VKORC1, CYP2C9*2, and CYP2C9*3 was done by polymerase chain reaction-restriction fragment length polymorphism. Bleeding and embolic complications were noted. The predictors of unstable INR were evaluated using multivariate analysis. Results: INR was stable in 47.8% and unstable in 52.2% of patients. Patients with mutant genotypes required low dose of acenocoumarin. The predictors of unstable INR were metallic valve (odds ratio [OR] 4.07, 95% confidence interval [CI] 1.23-13.49, P = 0.02), use of digoxin (OR 0.031, 95% CI 0.13-0.74, P = 0.09), proton pump inhibitor (OR 0.23, 95% CI 0.06-0.91, P = 0.037), sodium valproate (OR 0.22, 95% CI 0.05-0.85, P = 0.029), and CYP2C9*2 genotype (OR 5.57, 95% CI 1.19-26.06, P = 0.02). Conclusions: Variant genotypes of VKORC1, CYP2C9*2, and CYP2C9*3 required lower dose of acenocoumarin, and CYP2C9*2 was associated with unstable INR. Comedication is a modifiable risk factor that needs attention.
- Subjects
STROKE prevention; ANTICOAGULANTS; RISK assessment; PROTHROMBIN time; POLYMERASE chain reaction; TREATMENT effectiveness; MULTIVARIATE analysis; DESCRIPTIVE statistics; SINUS thrombosis; GENETIC polymorphisms; ODDS ratio; PHARMACOGENOMICS; CYTOCHROME P-450; OXIDOREDUCTASES; INTERNATIONAL normalized ratio; DIGOXIN; VALPROIC acid; DRUG interactions; COMPARATIVE studies; CONFIDENCE intervals; PROTON pump inhibitors; STROKE; GENOTYPES
- Publication
Annals of Indian Academy of Neurology, 2024, Vol 27, Issue 3, p274
- ISSN
0972-2327
- Publication type
Article
- DOI
10.4103/aian.aian_886_23