Publication: Estudio observacional sobre la influencia de la adherencia terapéutica en la efectividad y seguridad del tratamiento con anticoagulantes orales directos en fibrilación auricular
Authors
González Lozano, Eduardo
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Escuela Internacional de Doctorado
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Marín Ortuño, Francisco ; Rivera Caravaca, José Miguel
Publisher
Universidad de Murcia
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DOI
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info:eu-repo/semantics/doctoralThesis
Description
Abstract
Introducción y justificación.
La fibrilación auricular (FA) es la arritmia cardíaca más frecuente en la práctica clínica. Representa un problema de salud pública de primer orden, debido a su creciente prevalencia y a su asociación con una elevada morbimortalidad, principalmente derivada del riesgo de ictus cardioembólico e insuficiencia cardíaca. Aunque los anticoagulantes orales directos (ACODs) -apixabán, dabigatrán, edoxabán y rivaroxabán- se han establecido como la primera línea de tratamiento para la prevención del tromboembolismo debido a su perfil de seguridad y eficacia superior frente a los antagonistas de la vitamina K (AVK), su efectividad en el "mundo real" está intrínsecamente ligada a la adherencia terapéutica.
Objetivos y metodología.
Se diseñó un estudio observacional de cohortes retrospectivo con el objetivo principal de analizar la adherencia al tratamiento con ACODs y determinar su influencia en la efectividad (prevención de ictus isquémico o accidente isquémico transitorio [AIT]) y seguridad en pacientes con FA. Se incluyeron todos los pacientes con FA del Área I del Servicio Murciano de Salud (SMS) que iniciaron tratamiento con algún ACOD entre enero de 2016 y octubre de 2019, con un seguimiento de 2 años. La adherencia se evaluó mediante la Ratio de Posesión de Medicamentos (RPM), definiendo una adherencia adecuada como una RPM mayor o igual a 80. La persistencia se definió como la ausencia de interrupciones del tratamiento superiores a 60 días. Se emplearon modelos de regresión logística binaria y modelos de riesgos proporcionales de Cox (univariante y multivariante), para identificar factores predictores de mala adherencia y evaluar la asociación entre la adherencia y la aparición de eventos adversos.
Resultados.
La población final de estudio consistió en 2.209 pacientes, caracterizados por una mediana de edad avanzada (77 años), pluripatología y polimedicación. El perfil de riesgo fue elevado, con un 94,7% de los pacientes presentando un riesgo tromboembólico alto y un 49,6% un riesgo hemorrágico alto. En cuanto a la adecuación de dosis, se observó que el 23,4% de los pacientes recibía dosis inadecuadas, destacando el infratratamiento en pacientes con apixabán y el sobretratamiento con dabigatrán. Respecto a las variables primarias, el 9,5% de los pacientes presentó una adherencia inadecuada (RPM <80%) y el 17,9% una persistencia inadecuada a los 2 años (periodo de gracia de 60 días). El análisis multivariante identificó varios factores predictores independientes asociados a la mala adherencia: la edad menor de 65 años, la posología de dos veces al día, los antecedentes de hemorragia y el uso concomitante de antiagregantes. Por el contrario, la presencia de dislipemia actuó como un factor protector. En términos de resultados clínicos, los pacientes con mala adherencia (RPM <80%) presentaron una incidencia acumulada de ictus isquémico significativamente superior a los pacientes adherentes y una mayor mortalidad por cualquier causa. Tras el ajuste multivariante, la mala adherencia se confirmó como un predictor robusto e independiente, asociándose con un riesgo más de dos veces superior de sufrir un ictus isquémico/AIT a los 2 años. Otros factores predictivos de ictus/AIT fueron la edad avanzada y la presencia de enfermedad renal.
Conclusiones.
Este estudio concluye que, aunque la adherencia global a los ACODs en nuestro entorno es alta, existe un subgrupo de pacientes con adherencia subóptima, duplicando el riesgo de ictus. Por tanto, la evaluación continua de la adherencia debe integrarse como un pilar fundamental en el manejo clínico del paciente con FA anticoagulado.
Introduction and rationale. Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. It represents a major public health problem due to its increasing prevalence and its association with high morbidity and mortality, primarily stemming from the risk of cardioembolic stroke and heart failure.Although direct oral anticoagulants (DOACs)-apixaban, dabigatran, edoxaban, and rivaroxaban-have become the first-line treatment for thromboembolic prevention due to their superior safety and efficacy profile compared to vitamin K antagonists (VKAs), their effectiveness in the "real world" is intrinsically linked to therapeutic adherence. Objectives and methodology. A retrospective cohort study was designed with the primary objective of analyzing adherence to direct oral anticoagulant treatment and determining its influence on the effectiveness (prevention of ischemic stroke or transient ischemic attack [TIA]) and safety of patients with AF.All patients with AF from Area I of the Murcia Health Service who initiated treatment with any DOAC between January 2016 and October 2019 were included, with a 2-year follow-up. Adherence was assessed using the Medication Possession Ratio (MPR), defining adequate adherence as an MPR higher or equal than 80. Persistence was defined as the absence of treatment interruptions exceeding 60 days. Binary logistic regression models and Cox proportional hazards models (univariate and multivariate) were used to identify predictors of poor adherence and to evaluate the association between adherence and the occurrence of adverse events. Results. The final study population consisted of 2.209 patients, characterized by an advanced median age (77 years), multiple comorbidities, and polypharmacy. The risk profile was high, with 94,7% of patients presenting a high thromboembolic risk and 49,6% a high bleeding risk. Regarding dose adequacy, it was observed that 23,4% of patients received inadequate doses, notably undertreatment in patients receiving apixaban and overtreatment with dabigatran. Regarding the primary variables, 9,5% of patients presented inadequate adherence (RPM <80%) and 17,9% inadequate persistence at 2 years (60-day grace period). Multivariate analysis identified several independent predictors associated with poor adherence: age under 65 years (OR 2,079), twice-daily dosing (OR 1,522), history of bleeding (OR 1,603), and concomitant use of antiplatelet agents (OR 2,060). Conversely, the presence of dyslipidemia acted as a protective factor (OR 0,666). In terms of clinical outcomes, patients with poor adherence (PMR <80%) had a significantly higher cumulative incidence of ischemic stroke than adherent patients (5,7% vs 1,9%; p<0,001) and higher all-cause mortality (19,1% vs 11,2%; p<0,001). After multivariate adjustment, poor adherence was confirmed as a robust and independent predictor, associated with a more than twofold increased risk of ischemic stroke/TIA at 2 years (adjusted HR 2,206; 95% CI 1,261-3,860). Other predictive factors for stroke/TIA were advanced age and the presence of kidney disease. Conclusions. This study concludes that, although overall adherence to DOACs in our setting is high, there is a subgroup of patients with suboptimal adherence, doubling the risk of ischemic cerebrovascular events. Therefore, continuous assessment of adherence should be integrated as a fundamental pillar in the clinical management of the anticoagulated AF patient.
Introduction and rationale. Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. It represents a major public health problem due to its increasing prevalence and its association with high morbidity and mortality, primarily stemming from the risk of cardioembolic stroke and heart failure.Although direct oral anticoagulants (DOACs)-apixaban, dabigatran, edoxaban, and rivaroxaban-have become the first-line treatment for thromboembolic prevention due to their superior safety and efficacy profile compared to vitamin K antagonists (VKAs), their effectiveness in the "real world" is intrinsically linked to therapeutic adherence. Objectives and methodology. A retrospective cohort study was designed with the primary objective of analyzing adherence to direct oral anticoagulant treatment and determining its influence on the effectiveness (prevention of ischemic stroke or transient ischemic attack [TIA]) and safety of patients with AF.All patients with AF from Area I of the Murcia Health Service who initiated treatment with any DOAC between January 2016 and October 2019 were included, with a 2-year follow-up. Adherence was assessed using the Medication Possession Ratio (MPR), defining adequate adherence as an MPR higher or equal than 80. Persistence was defined as the absence of treatment interruptions exceeding 60 days. Binary logistic regression models and Cox proportional hazards models (univariate and multivariate) were used to identify predictors of poor adherence and to evaluate the association between adherence and the occurrence of adverse events. Results. The final study population consisted of 2.209 patients, characterized by an advanced median age (77 years), multiple comorbidities, and polypharmacy. The risk profile was high, with 94,7% of patients presenting a high thromboembolic risk and 49,6% a high bleeding risk. Regarding dose adequacy, it was observed that 23,4% of patients received inadequate doses, notably undertreatment in patients receiving apixaban and overtreatment with dabigatran. Regarding the primary variables, 9,5% of patients presented inadequate adherence (RPM <80%) and 17,9% inadequate persistence at 2 years (60-day grace period). Multivariate analysis identified several independent predictors associated with poor adherence: age under 65 years (OR 2,079), twice-daily dosing (OR 1,522), history of bleeding (OR 1,603), and concomitant use of antiplatelet agents (OR 2,060). Conversely, the presence of dyslipidemia acted as a protective factor (OR 0,666). In terms of clinical outcomes, patients with poor adherence (PMR <80%) had a significantly higher cumulative incidence of ischemic stroke than adherent patients (5,7% vs 1,9%; p<0,001) and higher all-cause mortality (19,1% vs 11,2%; p<0,001). After multivariate adjustment, poor adherence was confirmed as a robust and independent predictor, associated with a more than twofold increased risk of ischemic stroke/TIA at 2 years (adjusted HR 2,206; 95% CI 1,261-3,860). Other predictive factors for stroke/TIA were advanced age and the presence of kidney disease. Conclusions. This study concludes that, although overall adherence to DOACs in our setting is high, there is a subgroup of patients with suboptimal adherence, doubling the risk of ischemic cerebrovascular events. Therefore, continuous assessment of adherence should be integrated as a fundamental pillar in the clinical management of the anticoagulated AF patient.
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