Evaluation of implementation and optimization of a pharmacogenetic-based warfarin dosing algorithm in admixed populations

• Grant number: 22/05170-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2023
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Paulo Caleb Júnior de Lima Santos
• Grantee: Pedro Eduardo Nascimento Silva Vasconcelos
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Although warfarin is effective, it has a narrow therapeutic interval with difficult dose adjustment, and low TTR values (time within the therapeutic range <50%) are associated with risk of adverse events and, consequently, broad public spending. Studies show that clinical and genetic factors influence warfarin dose variability. Our group developed a pharmacogenetic algorithm estimating warfarin dose specific to our Brazilian population that proved more accurate than other international algorithms. Although we have studies in the literature on the pharmacogenetic approach in Brazil, the studies are retrospective and, to our knowledge, there are only initiatives for applicability assessments and randomized clinical studies for this purpose in the Brazilian population. In addition, there is also no study that determines the influence of local ancestry and check algorithms for admixed populations via machine learning. Thus, the aim of this project are to evaluate the implementation of the pharmacogenetic algorithm estimating warfarin dose, to determine the influence of local ancestry on the stable dose of warfarin and to optimize algorithms for admixed populations using machine learning. For the realization of this project, we have well established national and international collaborations. The patients will come from two centers: arrhythmia outpatient clinics of the Paulista School of Medicine of Unifesp and the Heart Institute of FMUSP. Analysis of local ancestry and optimization of algorithms for admixed populations will be carried out in conjunction with international collaborators Profa. Dr. Larisa Cavallari, Prof. Dr. Vakaramoko, University of Florida, USA, and Prof. Dr. Jason Karnes of the University of Arizona, USA. This pioneering study may estimate a possible decrease in thromboembolic and hemorrhagic events, which may indicate lower costs for Brazilian public health.