Evaluación del rendimiento de un modelo clínico-genético en la estimación del tiempo en rango terapéutico de pacientes con fibrilación auricular no valvular tratados con acenocumarol

Resumo

Evaluation of the Performance of a Clinical-Genetic model in the Estimation of Time in Therapeutic Range in patients with non-valvular atrial fibrillation treated with Acenocoumarol. Introduction: The efficacy and safety of treatment with vitamin K antagonists (VKA) in patients with atrial fibrillation (AF) strongly depends on the ability of achieving and maintaining an adequate level of anticoagulation. In spite of the introduction of direct oral anticoagulants, VKA remain the most used anticoagulant treatment in patients with AF world-wide. Quality of anticoagulation is assessed with time in therapeutic range (TTR) defined by Rosendaal, and although clinical trials present relatively high TTR, it seems that "real-world" control is not that strict. The SAMeTT2R2 score was proposed in order to identify those patients that would present a good response to VKA treatment. In the initial study the SAMeTT2R2 score showed a reasonable discrimination, that is a correct ability to identify patients with an adequate TTR. However, this score was elaborated from a group of patients with AF included in a clinical trial, and therefore a potential selection bias and other methodological limitations raise doubts about its applicability in clinical practice. Finally, some authors have proposed that TTR prediction could improve with the identification of genetic polymorphisms that have been found to be involved in the biotransformation mechanisms o VKA. Aims: - To analyze the quality of anticoagulation in patients with non-valvular AF in our cohort treated with acenocoumarol by means of TTR calculated by the Rosendaal method. - To assess the performance of the SAMeTT2R2 score in the prediction of TTR in our cohort. - To identify the clinical and genetic factors involved in a correct level of anticoagulation with VKA that could potentially improve the diagnostic performance of SAMeTT2R2 score. Methods: we included 212 consecutive patients with non-valvular atrial fibrillation under treatment with acenocoumarol for at least 6 months, that were attended in a Cardiology outpatient clinic and were categorized as adherent to medication. We carried out a multivariate regression analysis to detect the independent predictive factors of good anticoagulation control. In all patients VKORC1, CYP2C9*2, CYP2C9*3 and MIR133A2 genotyping was performed. Results: a total of 128 (60.4%) patients presented TTR <70% (average TTR = 63.2). We identified body mass index (OR 0.94, 95%CI 0.89 - 0.99, p=0.032) and regular vitamin K intake (OR 0.53, 95%CI 0.28 - 0.99, p= 0.046) as independent predictors of poor anticoagulation control. The discriminatory power of a clinical-genetic model derived from our cohort (that included body mass index, vitamin K intake and the analysed polymorphisms) was significantly better compared to the SAMeTT2R2score (C- statistic 0.658 vs. 0.524, p<0.001). Conclusions: the analysis of quality of anticoagulation with acenocoumarol in patients with non-valvular AF revealed a high proportion of patients with suboptimal control of such therapy in our cohort. The SAMeTT2R2 score revealed a poor ability to predict an adequate TTR. Clinical factors such as body mass index and vitamin K intake as well as the analysed genetic polymorphisms were capable of improving the discriminatory power of SAMeTT2R2 score.