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      The use and adherence of oral anticoagulants in Primary Health Care in Catalunya, Spain: A real-world data cohort study Translated title: Uso y adherencia a los anticoagulantes orales en Atención Primaria en Cataluña, España: estudio de cohortes con datos procedentes de registros electrónicos de salud

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          Abstract

          Objective

          We aimed to describe sociodemographic, comorbidities, co-medication and risk of thromboembolic events and bleeding in patients with NVAF initiating oral anticoagulants (OAC) for stroke prevention, and to estimate adherence and persistence to OAC.

          Setting

          Primary Health Care (PHC) in the Catalan Health Institute (ICS), Catalunya, Spain.

          Participants

          All NVAF adult patients initiating OAC for stroke prevention in August 2013–December 2015.

          Methods

          Population-based cohort study. Persistence was measured in patients initiating OAC in August 2013–December 2014.

          Data source: SIDIAP, which captures electronic health records from PHC in the (ICS), covering approximately 5.8 million people.

          Results

          51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 (62.7%) initiated acenocoumarol. Mean age was 72.8 years (SD 12.3) and 49.4% were women. Platelet-aggregation inhibitors were taken by 9105 (17.6%) of the patients. Persistence and adherence were estimated up to the end of follow-up. For 22,075 patients, persistence was higher among the non-naive patients [ n = 258 (61.7%)] than among the naive [ n = 11,502 (53.1%)]. Adherence was estimated for patients initiating DOAC and it was similar in naive and non-naive patients. Among the naive to DOAC treatment, those starting rivaroxaban showed a highest proportion [( n = 360 (80.1%)] of good adherence at implementation (MPR > 80%) while patients starting dabigatran were less adherent [ n = 203 (47.8%)].

          Conclusions

          Acenocoumarol was the most frequently prescribed OAC as first therapy in NVAF patients. Non-naive to DOAC showed better persistence than naive. Rivaroxaban showed higher proportion of adherent patients during the implementation phase than apixaban and dabigatran the lowest.

          Translated abstract

          Objetivo

          Describir datos sociodemográficos, comorbilidades, comedicaciones y riesgo de eventos tromboembólicos y hemorrágicos de los pacientes con fibrilación auricular no valvular (FANV) que inician tratamiento anticoagulante por vía oral (TAO) para prevención del ictus. Estimar adherencia y persistencia al TAO.

          Emplazamiento

          Atención primaria (AP) del Instituto Catalán de Salud (ICS), Cataluña, España.

          Participantes

          Adultos con FANV que inician TAO para prevención de ictus entre agosto del 2013 y diciembre del 2015.

          Métodos

          Estudio de cohortes de base poblacional. Adherencia y persistencia se midieron en pacientes que iniciaban TAO entre agosto del 2013 y diciembre del 2014.

          Fuente de datos: SIDIAP, base de datos procedentes de registros electrónicos de AP del ICS, que cubre aproximadamente una población de 5,8 millones de personas.

          Resultados

          Cincuenta y un mil seiscientos noventa pacientes con FANV iniciaron TAO, 47.197 (91,3%) eran naïve al TAO y 32.404 (62,7%) iniciaron acenocumarol. Su edad media era 72,8 años (DE 12,3) y el 49,4% eran mujeres; 90105 (17,6%) recibían tratamiento antiagregante plaquetario. Persistencia y adherencia se estimaron hasta el final del seguimiento. La persistencia a anticoagulantes orales directos (ACOD) fue mayor en no naïve que en naïve (61,7% vs. 53,1%). La adherencia a ACOD fue similar en los 2 grupos. Entre los naïve, los pacientes que iniciaban rivaroxabán (80,1%) mostraron mayor adherencia en la implementación (MPR > 80%), mientras que los que iniciaban dabigatrán fueron menos adherentes (47,8%).

          Conclusiones

          Acenocumarol fue el anticoagulante más prescrito. Los pacientes no naïve mostraron mejor persistencia al tratamiento que los naïve. Rivaroxabán mostró mayores tasas de adherencia que apixabán y dabigatrán, las menores.

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          Most cited references26

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          The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy).

          The goal of this study was to analyze the impact of dabigatran plasma concentrations, patient demographics, and aspirin (ASA) use on frequencies of ischemic strokes/systemic emboli and major bleeds in atrial fibrillation patients. The efficacy and safety of dabigatran etexilate were demonstrated in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, but a therapeutic concentration range has not been defined. In a pre-specified analysis of RE-LY, plasma concentrations of dabigatran were determined in patients treated with dabigatran etexilate 110 mg twice daily (bid) or 150 mg bid and correlated with the clinical outcomes of ischemic stroke/systemic embolism and major bleeding using univariate and multivariate logistic regression and Cox regression models. Patient demographics and ASA use were assessed descriptively and as covariates. Plasma concentrations were obtained from 9,183 patients, with 112 ischemic strokes/systemic emboli (1.3%) and 323 major bleeds (3.8%) recorded. Dabigatran levels were dependent on renal function, age, weight, and female sex, but not ethnicity, geographic region, ASA use, or clopidogrel use. A multiple logistic regression model (c-statistic 0.657, 95% confidence interval [CI]: 0.61 to 0.71) showed that the risk of ischemic events was inversely related to trough dabigatran concentrations (p = 0.045), with age and previous stroke (both p < 0.0001) as significant covariates. Multiple logistic regression (c-statistic 0.715, 95% CI: 0.69 to 0.74) showed major bleeding risk increased with dabigatran exposure (p < 0.0001), age (p < 0.0001), ASA use (p < 0.0003), and diabetes (p = 0.018) as significant covariates. Ischemic stroke and bleeding outcomes were correlated with dabigatran plasma concentrations. Age was the most important covariate. Individual benefit-risk might be improved by tailoring dabigatran dose after considering selected patient characteristics. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases.

            To propose a unifying set of definitions for prescription adherence research utilizing electronic health record prescribing databases, prescription dispensing databases, and pharmacy claims databases and to provide a conceptual framework to operationalize these definitions consistently across studies. We reviewed recent literature to identify definitions in electronic database studies of prescription-filling patterns for chronic oral medications. We then develop a conceptual model and propose standardized terminology and definitions to describe prescription-filling behavior from electronic databases. The conceptual model we propose defines 2 separate constructs: medication adherence and persistence. We define primary and secondary adherence as distinct subtypes of adherence. Metrics for estimating secondary adherence are discussed and critiqued, including a newer metric (New Prescription Medication Gap measure) that enables estimation of both primary and secondary adherence. Terminology currently used in prescription adherence research employing electronic databases lacks consistency. We propose a clear, consistent, broadly applicable conceptual model and terminology for such studies. The model and definitions facilitate research utilizing electronic medication prescribing, dispensing, and/or claims databases and encompasses the entire continuum of prescription-filling behavior. Employing conceptually clear and consistent terminology to define medication adherence and persistence will facilitate future comparative effectiveness research and meta-analytic studies that utilize electronic prescription and dispensing records.
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              Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation

              Background The introduction of non–vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. Methods and Results Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46–0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76–1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72–1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34–0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67–0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90–1.20], P=0.60). All non–vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. Conclusions In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin.
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                Author and article information

                Contributors
                Journal
                Aten Primaria
                Aten Primaria
                Atencion Primaria
                Elsevier
                0212-6567
                1578-1275
                09 August 2020
                October 2020
                09 August 2020
                : 52
                : 8
                : 529-538
                Affiliations
                [a ]Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
                [b ]Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain
                [c ]Institut Català de la Salut, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain
                [d ]Department d’Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Spain
                [e ]Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, Girona, Spain
                [f ]Department of Clinical Pharmacology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
                [g ]Department of Pathology and Experimental Therapeutics, Unitat Docent Campus de Bellvitge, Universitat de Barcelona, L’Hospitalet (Barcelona), Spain
                [h ]UICEC IDIAP Jordi Gol, Plataforma SCReN, Barcelona, Spain
                Author notes
                [* ]Corresponding author. agomez@ 123456idiapjgol.info
                Article
                S0212-6567(20)30184-0
                10.1016/j.aprim.2020.05.016
                7505898
                32788057
                02db31f1-b30a-4104-a975-3f465163bc59
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 3 March 2020
                : 21 May 2020
                Categories
                Original Article

                atrial fibrillation,oral anticoagulants,adherence,persistence,electronic health records,fibrilación auricular,tratamiento anticoagulante oral,adherencia,persistencia,registros electrónicos de salud

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