Avaliação dos fatores de risco associados ao controle inadequado da anticoagulação oral: estudo observacional.

Abstract

Warfarin is indicated for primary and secondary thromboprophylaxis in cardiovascular diseases. However, its response varies between patients, requiring periodic laboratory monitoring. The quality of anticoagulant therapy may be analyzed using the time in therapeutic range (TTR), which is recommended to be above 60%. Maintaining an adequate TTR depends on the warfarin characteristics, patient-related factors, and healthcare services. Studies on the subject have shown conflicting results and are scarce in Brazil. The objective of this study was to evaluate the risk factors associated with inadequate oral anticoagulation control in patients treated at three public anticoagulation clinics in Belo Horizonte, Minas Gerais. Two cross-sectional studies were conducted with patients using warfarin recruited from 2014 to 2015, resulting in two articles. The quality of oral anticoagulation was estimated by TTR. The aim of the first article was to investigate the association of sex with oral anticoagulation control. Adult patients (≥18 years) of both sexes with a definitive diagnosis of heart disease and at least one indication for continuous warfarin use for at least two months (e.g., atrial fibrillation (AF) and mechanical heart valve prosthesis) were included. Patients with anticipated warfarin use for less than 12 months, life expectancy of less than one year, inability to communicate, and lack of caregiver involvement were excluded. The association of sociodemographic, behavioral, clinical, and drug therapy variables with TTR was examined using univariable and multivariable linear regression models. In total, 801 participants (455; 56.8% women) with a mean age of 65.0±13.4 years was evaluated. Women had a lower TTR than men [Beta (95% CI)=-17.01 (-30.25; -3.76), p=0.012], however, this difference decreased with increasing age, becoming null after 60 years. The aim of the second article was to evaluated the role of polymorphisms in the CYP2C9 (*1, *2 and *3), VKORC1 (-1639G>A), MDR1 (3435C>T) and APOE (ε2, ε3 and ε4) genes, as well as clinical factors, in the control of oral anticoagulation in older patients. The inclusion and exclusion criteria were the same as in article 1, except for age. This article included participants aged ≥60 years. Two decision tree models were developed (one including clinical and genetic factors and the other restricted to clinical variables). The performance of the models was assessed using R-squared. A total of 209 patients (mean age 71.6±7.2 years) was studied. Carriers of the VKORC1 GG genotype had a lower TTR than carriers of the VKORC1 AA and VKORC1 GA genotypes (63.5%, 67.8% and 70.9%, respectively; p=0.012). The model including clinical and genetic factors suggested a greater capacity to explain the variability in TTR (R-squared=0.352) compared to the model including only clinical variables (Rsquared=0.262). Genetic polymorphisms may impact the control of oral anticoagulation with warfarin in older patients. The results may contribute to the development of strategies aimed at optimization warfarin therapy, as well as supporting the development of larger studies on the subject in other populations.