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.