SAMe-TT2R2 score for prediction of suboptimal time in therapeutic range in a Thai population with atrial fibrillation

INTRODUCTION@#International normalised ratio (INR) control is an important factor in patients with non-valvular atrial fibrillation (NVAF) being treated with warfarin. INR control was previously reported to be poorer among Asians compared to Westerners. We aimed to validate the SAMe-TT2R2 score for prediction of suboptimal INR control (defined as time in therapeutic range [TTR] < 65% in the Thai population) and to investigate TTR among Thai NVAF patients being treated with warfarin.@*METHODS@#INR data from patients enrolled in a multicentre NVAF registry was analysed. Clinical and laboratory data was prospectively collected. TTR was calculated using the Rosendaal method. Baseline data was compared between patients with and without suboptimal INR control. Univariate and multivariate analyses were performed to identify variables independently associated with suboptimal INR control.@*RESULTS@#A total of 1,669 patients from 22 centres located across Thailand were included. The average age was 69.1 ± 10.7 years, and 921 (55.2%) were male. The mean TTR was 50.5% ± 27.5%; 1,125 (67.4%) had TTR < 65%. Univariate analysis showed hypertension, diabetes mellitus, heart failure, renal disease and SAMe-TT2R2 score to be significantly different between patients with and without optimal TTR. The SAMe-TT2R2 score was the only factor that remained statistically significant in multivariate analysis. The C-statistic for the SAMe-TT2R2 score in the prediction of suboptimal TTR was 0.54.@*CONCLUSION@#SAMe-TT2R2 score was the only independent predictor of suboptimal TTR in NVAF patients being treated with warfarin. However, due to the low C-statistic, the score may have limited discriminative power.

Evaluación del SAME-TT2R2 score en la calidad de la anticoagulación con warfarina / Evaluation of SAME-TT2R2 score on the quality of anticoagulation with warfarin

Resumen Introducción: la fibrilación auricular (FA) es la arritmia cardiaca más frecuente y está relacionada con eventos embólicos. La eficacia y seguridad de la warfarina en prevención del ictus depende del tiempo en rango terapéutico (TTR). Se han diseñado escalas para predecir el comportamiento del TTR al inicio de la terapia. El objetivo de este trabajo fue evaluar la capacidad predictiva y discriminativa del SAMeTT2R2 score en una población no caucásica. Material y métodos: estudio analítico de cohorte retrospectiva en pacientes con FA no valvu lar tratados con warfarina entre 2013 y 2016 en una clínica de anticoagulación. Se caracterizó la muestra sociodemográfica y clínicamente. Se definió mal control de la anticoagulación como (TTR/ PINNR<65%). Se comparó el TTR/PINNR <65% y SAMeTT2R2 <=2 versus >2 con la prueba U de Mann-Whitney y chi cuadrado. Se construyeron curvas ROC para determinar discriminación de la escala. Se evaluó cada uno de sus elementos a través de regresión logística. Resultados: se incluyeron 646 pacientes (edad media 77 años ± 8,8 años, 51,4% hombres). El TTR promedio fue 67.7% y el PINNR 63.6%. Al comparar la frecuencia de pobre control entre SAMeTT2R2 score ≤2 versus >2 con una prueba chi cuadrado, el PINNR fue significativo (p=0.004). La capacidad discriminativa de la escala para el TTR/PINNR fue baja (AUC: 0.52 y 0.54 respectivamente). No se encontró relación entre cada una de las variables que integran el SAMeTT2R2 score y el TTR/PINNR. Conclusiones: la puntuación SAMeTT2R2 no mostró buena capacidad predictiva y discriminativa en la población estudiada. La calidad de la anticoagulación es el resultado de un proceso dinámico en relación con el cumplimiento, estado de salud o enfermedad intercurrente. (Acta Med Colomb 2019; 44: 75-81).

Abstract Introduction: atrial fibrillation (AF) is the most common cardiac arrhythmia and is related to embolic events. The efficacy and safety of warfarin in stroke prevention depends on the time in therapeutic range (TTR). Scales have been designed to predict the behavior of TTR at the start of therapy. The objective of this work was to evaluate the predictive and discriminative capacity of the SAMeTT2R2 score in a non-Caucasian population. Material and methods: retrospective cohort analytical study in patients with non-valvular AF treated with warfarin between 2013 and 2016 in an anticoagulation clinic. The sample was demodemographically and clinically characterized. Poor control of anticoagulation was defined as (TTR / PINNR <65%). The TTR / PINNR <65% and SAMeTT2R2 <= 2 versus> 2 were compared with the Mann-Whitney U test and chi square. ROC curves were constructed to determine scale discrimination. Each of its elements was evaluated through logistic regression. Results: 646 patients were included (mean age 77 years ± 8.8 years, 51.4% men). The average TTR was 67.7% and the PINNR 63.6%. When comparing the frequency of poor control between C. L. Sandoval-Riveros y cols. SAMeTT2R2 score ≤2 versus> 2 with a chi square test, the PINNR was significant (p = 0.004). The discriminative capacity of the scale for the TTR / PINNR was low (AUC: 0.52 and 0.54 respec tively). No relationship was found between each of the variables that constitute the SAMeTT2R2 score and the TTR / PINNR. Conclusions: the SAMeTT2R2 score did not show good predictive and discriminative capac ity in the studied population. The quality of anticoagulation is the result of a dynamic process in relation to compliance, health status or intercurrent disease. Acta Med Colomb 2019; 44: 75-81).

Utilidad del score SAMe-TT2R2 en el control de la anticoagulación oral con warfarina en pacientes con fibrilación auricular no valvular / Usefulness of the SAMe-TT2R2 score in the control of oral anticoagulation with warfarin in patients with non-valvular atrial fibrillation

Antecedentes: la prevención de eventos tromoboembólicos mediante anticoagulación oral es uno de los principales objetivos en el tratamiento de la fibrilación auricular (FA) no valvular, pudiendo utilizarse tanto fármacos antivitamina K (AVK), como warfarina y anticoagulantes orales directos (ACOD). La warfarina ofrece su mayor eficacia y seguridad cuando el porcentaje de tiempo en rango terapéutico (TTR) es mayor de 65%-70%. El score SAMe-TT2R2 fue desarrollado como herramienta para intentar predecir la respuesta al tratamiento anticoagulante con fármacos AVK. Los pacientes con un puntaje favorable (0-1 punto) tendrían una buena respuesta al tratamiento y por lo tanto un TTR adecuado, mientras que un puntaje desfavorable (2 puntos) permitiría predecir un TTR inadecuado, identificando pacientes que requieren intervenciones adicionales para optimizar la calidad de anticoagulación o que serían mejores candidatos a ACOD. Objetivo: evaluar la utilidad del score SAMe-TT2R2 en el control de la anticoagulación oral con warfarina en pacientes portadores de FA no valvular. Método: estudio retrospectivo de 115 pacientes ambulatorios con FA no valvular, anticoagulados con warfarina entre el 1° de junio de 2012 y el 31 de junio de 2014. Las variables analizadas fueron: edad, sexo, fracción de eyección del ventrículo izquierdo (FEVI), comorbilidades, fármacos concomitantes, score CHA2DS2-VASc y HAS-BLED. Se calculó el TTR individual mediante método de Rosendaal y se calculó el score SAMe-TT2R2. Se utilizó el test de t para comparación de medias y el test de chi² para análisis de variables categóricas. Se consideró significativo un valor p<0,05. Resultados: la media de edad fue de 71,0±9,8 años, sexo masculino 52,2%. Comorbilidades asociadas fueron: hipertensión arterial (HTA) 82,6%, cardiopatía isquémica 24,3%, diabetes mellitus 18,3%, ataque cerebrovascular previo 10,4%, tabaquismo 6,1% y ex tabaquista 30,4%, consumo concomitante de tres o más fármacos 87,0%. La media de FEVI fue de 48,3±12,4%, score CHA2DS2-VASc 3,6±1,2 puntos y score HAS-BLED 1,8±0,9 puntos. La media de TTR calculada fue de 54,9±21,6% y solamente 37 pacientes (32,2%) tuvieron un TTR 65%. El score SAMe-TT2R2 tuvo una media de 1,8±1,0 puntos, 45 pacientes (39,1%) tuvieron un puntaje favorable a warfarina (0-1 punto) y 70 pacientes (60,9%) un puntaje desfavorable (2 puntos). No hubo diferencia significativa en la media de TTR según la categoría de SAMe-TT2R2 (53,0±23,7% vs 56,2±20,2%, p=0,447). Tampoco se encontró asociación entre un score SAMe-TT2R2 favorable a warfarina y un TTR 65% (33,3% vs 31,4%, p=0,831). Conclusión: en la población estudiada no hubo diferencia en la calidad de la anticoagulación oral con warfarina entre las categorías (favorable y desfavorable) del score SAMe-TT2R2.

Background: prevention of thromboembolic events is the main objective of oral anticoagulation treatment in non-valvular atrial fibrillation (AF) and either oral anticoagulation with vitamin K antagonists (VKA), like warfarin, or direct oral anticoagulants (ACOD) can be used. When warfarin is used, a time in therapeutic range (TTR) >65- 70% offers the best efficacy and safety. The SAMe-TT2R2 score has been developed as a tool to predict the response to VKA. A favorable SAMe-TT2R2 score (0-1 point) can identify patients that respond adequately to VKA and will have a better TTR, whilst a not favorable SAMe-TT2R2score (2 points) associates with poor TTR, needing additional therapies to optimize anticoagulation quality control or would be better candidates to direct oral anticoagulants (ACOD) Objective: assess SAMe-TT2R2 score value in anticoagulation quality control of patients with non-valvular AF treated with warfarin. Method: retrospective study of 115 ambulatory patients with non-valvular AF receiving oral anticoagulation treatment with warfarin, from June 1st 2012 to June 31st 2014. Analyzed variables were age, sex, left ventricle ejection fraction (LVEF), comorbidities, number of concomitant drugs, CHA2DS2-VASc and HAS-BLED scores. Rosendaal method was used to calculate the individual TTR. Student T test was used to compare mean values and X2 test for categorical variables. P < 0.05 was considered statistically significant. Results: mean age was 71.0 ± 9.8 years, 52.2% were male, most frequent comorbidities were: hypertension 82.6%, ischemic heart disease 24.3%, diabetes mellitus 18.3%, cerebrovascular disease 10.4%, smoking 6.1% and former smoking 30.4%, concomitant use of 3 or more drugs 87%. Mean LVEF was 48.3 ± 12.5 %, CHA2DS2-VASc Score 3.6 ± 1.2 points and HAS-BLED Score 1.8 ± 0.9 points. Mean TTR was 54.9 ± 21.6% and only 37 patients (32.2%) had a TTR  65%. Mean SAMe-TT2R2 score was 1.8 ± 1.0 points, a warfarin-favorable score (0-1 point) was found in 45 patients (39.1%) and 70 patients (60.9%) had a non-favorable score (2 points). No significant mean TTR difference was found among SAMe-TT2R2 categories (53.0 ± 23.7% vs. 56.2 ± 20.2%, p=0.447). No association between a favorable SAMe-TT2R2 Score and a high TTR (65%) was found (33.3 vs. 31.4%, p=0.831). Conclusion: no difference in anticoagulation quality control was found among favorable and non-favorable SAMe-TT2R2 score categories.

Lack of Association of Clinical Factors (SAMe-TT2R2) with CYP2C9/VKORC1 Genotype and Anticoagulation Control Quality / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Advantages of new oral anticoagulations may be greater in atrial fibrillation (AF) patients of poor anticoagulation control with warfarin. The SAMe-TT2R2 scoring system, based on clinical variables, was recently developed to aid in identifying these patients. In this study, we investigated the association of this clinical composite score with genetic factors related warfarin dosing and the quality of anticoagulation control. METHODS: Clinical and genetic data were collected from 380 consecutive Korean patients with AF (CHA2DS2-VASc score, 3.5+/-1.8) who were followed for an average of 4 years. We evaluated factors associated with time in therapeutic range (TTR, INR 2-3), including the CYP2C9 and VKORC1 genotypes and the SAMe-TT2R2 score (Sex female, Age two co-morbidities], Treatment [interacting drugs, e.g., amiodarone], Tobacco use within 2 years [doubled], and Race non-white [doubled]). RESULTS: The average SAMe-TT2R2 score was 3.4+/-0.9, range 2-7; and 153 patients (40.2%) had SAMe-TT2R2 scores > or =4. Time in specific INR ranges varied depending on the VKORC1 genotype but not with the CYP2C9 genotype or the SAMe-TT2R2 score. TTR was higher in patients with the VKORC1 1173C>T than in VKORC1 TT (61.7+/-16% vs. 56.7+/-17.4%, P=0.031). Multivariate testing showed that VKORC1 genotype but not the SAMe-TT2R2 score was significantly associated with labile INRs. There was no correlation between the SAMe-TT2R2 scores and pharmacogenetic data. CONCLUSIONS: A genetic factor, but none of the common clinical and demographic factors, as combined in the SAMe-TT2R2 score, was associated with the quality of anticoagulation control in Korean patients with AF.