Identification of environmental and genetic factors that influence warfarin time in therapeutic range

Abstract

Warfarin is an oral anticoagulant prescribed to prevent and treat thromboembolic disorders. It has a narrow therapeutic window and must have its effect controlled. Prothrombin test, expressed in INR value, is used for dose management. Time in therapeutic range (TTR) is an important outcome of quality control of anticoagulation therapy and is influenced by several factors. The aim of this study was to identify genetic, demographic, and clinical factors that can potentially influence TTR. In total,422 patients using warfarin were investigated. Glibenclamide co-medication and presence of CYP2C9*2 and/or *3 alleles were associated with higher TTR, while amiodarone, acetaminophen and verapamil co-medication were associated with lower TTR. Our data suggest that TTR is influenced by co-medication and genetic factors. Thus, individuals in use of glibenclamide may need a more careful monitoring and genetic testing (CYP2C9*2 and/or *3 alleles) may improve the anticoagulation management. In addition, in order to reach and maintain the INR in the target for a longer period, it is better to discuss dose adjustment in office instead of by telephone assessment. Other studies are needed to confirm these results and to find more variables that could contribute to this important parameter.This can be prevented by avoiding warfarin over-or under-dosing. Moreover, the lowest percentage of time that patient spend in target INR is associated with bleeding, stroke and/or mortality (Connolly et al., 2008). Several factors can influence TTR, among them, therapy duration, the site where anticoagulation is monitored, type of manage-

Warfarin Pharmacogenomics for Precision Medicine in Real-Life Clinical Practice in Southern Africa: Harnessing 73 Variants in 29 Pharmacogenes

“…Hypertension was a predominant concurrent illness in our study cohort and is known to be a major illness among Africans, most of the time asymptomatically in males (Mutowo et al, 2015 ). Similarly, hypertension was a predominant comorbidity in similar studies in Sweden (Rydberg et al, 2020 ), South Africa (Njovane and Fasinu, 2012 ; Sonuga et al, 2016 ), and Brazil (Botton et al, 2020 ).…”

Genetic Associations With Stable Warfarin Dose Requirements in Han Chinese Patients

“…Earlier studies have shown that a number of demographic, clinical, and genetic factors all affect the warfarin maintenance dosage in patients. 7,8 A few warfarin dosing algorithms have incorporated genetic and environmental factors that affect stable warfarin dose requirements and predict the efficacy of treatment. 3,9 In particular, genetic variations have been found to play a key role in influencing the maintenance dose of warfarin.…”