Low Performance of a Clinical-Genetic Model in the Estimation of Time in Therapeutic Range in Acenocoumarol-Adherent Patients with Nonvalvular Atrial Fibrillation: The Quality of Anticoagulation Challenge

BACKGROUND: Anticoagulation with vitamin K antagonists continues to be a challenging task given the difficulty of achieving a correct time in therapeutic range (TTR). The SAMeTT(2)R(2) score has been proposed to identify patients that will be good responders. In this study we aimed to analyse clinical and genetic factors involved in a correct level of anticoagulation in patients with atrial fibrillation and thereby potentially improve the diagnostic performance of SAMeTT(2)R(2) score. METHODS: We prospectively included 212 consecutive patients with nonvalvular 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 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 was significantly better compared to the SAMeTT(2)R(2) score (C-statistic 0.658 versus 0.524, p<0.001). CONCLUSIONS: In our study the SAMeTT(2)R(2) score revealed a poor ability in the prediction of TTR. Besides SAMeTT(2)R(2), body mass index and possibly vitamin K intake should be taken into account when deciding the optimal anticoagulation strategy. The information provided by the identified genotypes was marginal.