A proposal of personalized medicine according to pharmacogenetic profile for elderly patients taking warfarin

• Grant number: 19/20993-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2020
• End date: January 31, 2021
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Mario Hiroyuki Hirata
• Grantee: Vitor Pitta Rodrigues
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Warfarin is effective and the most common anticoagulant used for the treatment and prevention of thromboembolic disorders. However, it is difficult to establish the optimal weekly dose of warfarin due to its narrow therapeutic range and high risk of bleeding. The most used test to control oral anticoagulation is prothrombin time, by calculating the international normalized ratio (INR). Older people require effective monitoring due to inherent to age factors like the use of concomitant medications, dietary vitamin K intake and heart diseases, which leads to variability in response and in the dose of warfarin required to achieve the target INR. Although it is known that genetic factors influence the therapeutic response to warfarin, in most Brazilian hospitals pharmacogenetic analysis is not yet considered in dose adjustment. Thus, the aim of this study is to evaluate the association between VKORC1, CYP2C9 and CYP4F2 polymorphisms and the weekly maintenance dose of warfarin in elderly patients. The study population will consist of 101 warfarin patients recruited from Dante Pazzanese Institute of Cardiology. The inclusion criteria include 70 years or older warfarin intake patients visit the anticoagulation clinic regularly and achieved the stabilization phase of therapy (INR values between 2 and 3) with the same weekly warfarin dose for at least three consecutive visits. Genotype analysis will be performed by real-time PCR using TaqMan" Sample-to SNP" and TaqMan® SNP Genotyping Assay detection system. The Statistical Package for the Social Sciences version 22.0 will be used for statistical analyzes. P value <0.05 will be considered significant. (AU)