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.
Highlights
Oral anticoagulants are extensively used in clinical practice to prevent and treat thromboembolic disorders (Hylek, 2013)
Patients followed by an office appointment had higher therapeutic range (TTR) than those followed by telephone calls
A previous study showed that patients monitored by telephone have higher levels of extreme out-ofrange International Normalized Ratio (INR) than patients monitored in office (Stoudenmire et al, 2014), which corroborates with our findings
Summary
Oral anticoagulants are extensively used in clinical practice to prevent and treat thromboembolic disorders (Hylek, 2013). Coumarins are the most used class of oral anticoagulants. Warfarin is the main oral anticoagulant prescribed worldwide. It is a vitamin K antagonist (VKA) that competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), which is an essential enzyme for the coagulation cascade. Vitamin K is an important cofactor to activate the procoagulant factors II, VII, IX, and X. Its effect is measured by the International Normalized Ratio (INR) value using the prothrombin test. Warfarin has a narrow therapeutic window, its effect must be strictly controlled (Ageno et al, 2012)
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