Svjetlana Supe1, Nada Božina2, Vesna Matijević3, Antonela Bazina3, Antonija Mišmaš3, Josip Ljevak3, Domagoj Alvir3, Mario Habek4, Zdravka Poljaković4. 1. Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia. Electronic address: ssupe2@hotmail.com. 2. Clinical Institute of Laboratory Diagnosis, Zagreb University Hospital Center, Department of Pharmacology, Zagreb, Croatia; University of Zagreb, School of Medicine, Croatia. 3. Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia. 4. Department of Neurology, Intensive Care Unit, University Hospital Center Zagreb, Zagreb, Croatia; University of Zagreb, School of Medicine, Croatia.
Abstract
BACKGROUND: Data on the prevalence of CYP2C9 and VKORC1 genes and their influence on anticoagulant effect and warfarin dose in stroke patients are scarce. The aim of this study was to determine the occurrence and significance of these gene polymorphisms and to establish pharmacogenetic algorithm to estimate the dose of introduction. Also, the goal was to determine tailored safety and intensity of anticoagulation response depending on the allelic variants and their impact on the clinical outcome in acute stroke patients in Croatia. METHODS: A total of 106 consented acute stroke patients were tested for CYP2C9 2, 3 and VKORC1 1173C>T gene polymorphisms. We estimated the dose of introduction and monitored anticoagulant effect obtained by INR values, time to reach stable dose, stable maintenance dose, time spent within the therapeutic/supratherapeutic INR range, occurrence of dosage side effects and clinical outcome depending on genotypes. RESULTS: We found that 83% of stroke patients in our study were carriers of multiple allelic variants. The predicted initial dose correlated with the stable warfarin maintenance dose (p=0.0311) and we correctly estimated the dose for 81.5% of 61.3% of study patients who required higher/lower doses than average. Warfarin dosage complications were slightly more frequent among the carriers of CYP2C9 2, 3 compared to the carriers of VKORC1 1173T alleles (68. 9% versus 62.5%), but their occurrence did not affect the final clinical outcome. CONCLUSION: Our data indicated rapid and safe anticoagulation achieved by using pharmacogenetically-predicted warfarin dose in high-risk acute stroke patients without increasing the risk of warfarin dosage complications in an elderly population.
BACKGROUND: Data on the prevalence of CYP2C9 and VKORC1 genes and their influence on anticoagulant effect and warfarin dose in strokepatients are scarce. The aim of this study was to determine the occurrence and significance of these gene polymorphisms and to establish pharmacogenetic algorithm to estimate the dose of introduction. Also, the goal was to determine tailored safety and intensity of anticoagulation response depending on the allelic variants and their impact on the clinical outcome in acute strokepatients in Croatia. METHODS: A total of 106 consented acute strokepatients were tested for CYP2C9 2, 3 and VKORC1 1173C>T gene polymorphisms. We estimated the dose of introduction and monitored anticoagulant effect obtained by INR values, time to reach stable dose, stable maintenance dose, time spent within the therapeutic/supratherapeutic INR range, occurrence of dosage side effects and clinical outcome depending on genotypes. RESULTS: We found that 83% of strokepatients in our study were carriers of multiple allelic variants. The predicted initial dose correlated with the stable warfarin maintenance dose (p=0.0311) and we correctly estimated the dose for 81.5% of 61.3% of study patients who required higher/lower doses than average. Warfarin dosage complications were slightly more frequent among the carriers of CYP2C9 2, 3 compared to the carriers of VKORC1 1173T alleles (68. 9% versus 62.5%), but their occurrence did not affect the final clinical outcome. CONCLUSION: Our data indicated rapid and safe anticoagulation achieved by using pharmacogenetically-predicted warfarin dose in high-risk acute strokepatients without increasing the risk of warfarin dosage complications in an elderly population.