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array:23 [ "pii" => "S0300289620302672" "issn" => "03002896" "doi" => "10.1016/j.arbres.2020.07.032" "estado" => "S300" "fechaPublicacion" => "2021-03-01" "aid" => "2590" "copyright" => "SEPAR" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2021;57:205-13" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0300289620302805" "issn" => "03002896" "doi" => "10.1016/j.arbres.2020.08.001" "estado" => "S300" "fechaPublicacion" => "2021-03-01" "aid" => "2599" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2021;57:214-23" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Patterns of Physical Activity Progression in Patients With COPD" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "214" "paginaFinal" => "223" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Patrones de progresión de la actividad física en pacientes con EPOC" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 750 "Ancho" => 1333 "Tamanyo" => 70218 ] ] ] ] "autores" => array:3 [ 0 => array:2 [ "autoresLista" => "Maria Koreny, Heleen Demeyer, Marta Benet, Ane Arbillaga-Etxarri, Eva Balcells, Anael Barberan-Garcia, Elena Gimeno-Santos, Nicholas S. Hopkinson, Corina De Jong, Niklas Karlsson, Zafeiris Louvaris, Michael I. Polkey, Milo A. Puhan, Roberto A. Rabinovich, Robert Rodríguez-Roisin, Pere Vall-Casas, Ioannis Vogiatzis, Thierry Troosters, Judith Garcia-Aymerich" "autores" => array:20 [ 0 => array:2 [ "nombre" => "Maria" "apellidos" => "Koreny" ] 1 => array:2 [ "nombre" => "Heleen" "apellidos" => "Demeyer" ] 2 => array:2 [ "nombre" => "Marta" "apellidos" => "Benet" ] 3 => array:2 [ "nombre" => "Ane" "apellidos" => "Arbillaga-Etxarri" ] 4 => array:2 [ "nombre" => "Eva" "apellidos" => "Balcells" ] 5 => array:2 [ "nombre" => "Anael" "apellidos" => "Barberan-Garcia" ] 6 => array:2 [ "nombre" => "Elena" "apellidos" => "Gimeno-Santos" ] 7 => array:2 [ "nombre" => "Nicholas S." "apellidos" => "Hopkinson" ] 8 => array:2 [ "nombre" => "Corina" "apellidos" => "De Jong" ] 9 => array:2 [ "nombre" => "Niklas" "apellidos" => "Karlsson" ] 10 => array:2 [ "nombre" => "Zafeiris" "apellidos" => "Louvaris" ] 11 => array:2 [ "nombre" => "Michael I." "apellidos" => "Polkey" ] 12 => array:2 [ "nombre" => "Milo A." "apellidos" => "Puhan" ] 13 => array:2 [ "nombre" => "Roberto A." "apellidos" => "Rabinovich" ] 14 => array:2 [ "nombre" => "Robert" "apellidos" => "Rodríguez-Roisin" ] 15 => array:2 [ "nombre" => "Pere" "apellidos" => "Vall-Casas" ] 16 => array:2 [ "nombre" => "Ioannis" "apellidos" => "Vogiatzis" ] 17 => array:2 [ "nombre" => "Thierry" "apellidos" => "Troosters" ] 18 => array:2 [ "nombre" => "Judith" "apellidos" => "Garcia-Aymerich" ] 19 => array:1 [ "colaborador" => "The Urban Training Study Group and PROactive Consortium members" ] ] ] 1 => array:2 [ "autoresLista" => "" "autores" => array:1 [ 0 => array:1 [ "colaborador" => "The Urban Training Study Group" ] ] ] 2 => array:2 [ "autoresLista" => "" "autores" => array:1 [ 0 => array:1 [ "colaborador" => "The PROactive Consortium members" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0015"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289620302805?idApp=UINPBA00003Z" "url" => "/03002896/0000005700000003/v2_202106060540/S0300289620302805/v2_202106060540/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0300289620301162" "issn" => "03002896" "doi" => "10.1016/j.arbres.2020.03.034" "estado" => "S300" "fechaPublicacion" => "2021-03-01" "aid" => "2466" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2021;57:195-204" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Telerehabilitation Programme as a Maintenance Strategy for COPD Patients: A 12-Month Randomized Clinical Trial" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "195" "paginaFinal" => "204" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Programa de telerrehabilitación como estrategia de mantenimiento para pacientes con EPOC: un ensayo clínico aleatorizado de 12 meses" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0015" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 833 "Ancho" => 1333 "Tamanyo" => 113163 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan B. Galdiz, Alba Gómez, Diego Rodriguez, Rosa Guell, Pilar Cebollero, Javier Hueto, Pilar Cejudo, Francisco Ortega, Itxaso Sayago, Susana Chic, Marta Iscar, Carlos Amado, Gemma Rodríguez Trigo, Borja G. Cosio, Victor Bustamante, José Ignacio Pijoan" "autores" => array:16 [ 0 => array:2 [ "nombre" => "Juan B." "apellidos" => "Galdiz" ] 1 => array:2 [ "nombre" => "Alba" "apellidos" => "Gómez" ] 2 => array:2 [ "nombre" => "Diego" "apellidos" => "Rodriguez" ] 3 => array:2 [ "nombre" => "Rosa" "apellidos" => "Guell" ] 4 => array:2 [ "nombre" => "Pilar" "apellidos" => "Cebollero" ] 5 => array:2 [ "nombre" => "Javier" "apellidos" => "Hueto" ] 6 => array:2 [ "nombre" => "Pilar" "apellidos" => "Cejudo" ] 7 => array:2 [ "nombre" => "Francisco" "apellidos" => "Ortega" ] 8 => array:2 [ "nombre" => "Itxaso" "apellidos" => "Sayago" ] 9 => array:2 [ "nombre" => "Susana" "apellidos" => "Chic" ] 10 => array:2 [ "nombre" => "Marta" "apellidos" => "Iscar" ] 11 => array:2 [ "nombre" => "Carlos" "apellidos" => "Amado" ] 12 => array:2 [ "nombre" => "Gemma" "apellidos" => "Rodríguez Trigo" ] 13 => array:2 [ "nombre" => "Borja G." "apellidos" => "Cosio" ] 14 => array:2 [ "nombre" => "Victor" "apellidos" => "Bustamante" ] 15 => array:2 [ "nombre" => "José Ignacio" "apellidos" => "Pijoan" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0015"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289620301162?idApp=UINPBA00003Z" "url" => "/03002896/0000005700000003/v2_202106060540/S0300289620301162/v2_202106060540/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Treatment Pathways Before and After Triple Therapy in COPD: A Population-based Study in Primary Care in Spain" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "205" "paginaFinal" => "213" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Mònica Monteagudo, Alexa Nuñez, Iryna Solntseva, Nafeesa Dhalwani, Alison Booth, Miriam Barrecheguren, Dimitra Lambrelli, Marc Miravitlles" "autores" => array:8 [ 0 => array:3 [ "nombre" => "Mònica" "apellidos" => "Monteagudo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 1 => array:3 [ "nombre" => "Alexa" "apellidos" => "Nuñez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 2 => array:3 [ "nombre" => "Iryna" "apellidos" => "Solntseva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Nafeesa" "apellidos" => "Dhalwani" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 4 => array:3 [ "nombre" => "Alison" "apellidos" => "Booth" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Miriam" "apellidos" => "Barrecheguren" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 6 => array:3 [ "nombre" => "Dimitra" "apellidos" => "Lambrelli" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 7 => array:4 [ "nombre" => "Marc" "apellidos" => "Miravitlles" "email" => array:1 [ 0 => "marcm@separ.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Primary Care University Research Institute Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Pneumology Department, Hospital Universitari Vall d́Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus. CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Medicine Department, Autonomous University of Barcelona (UAB), Bellaterra (Cerdanyola del Vallés), Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Evidera, London, UK" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vías de tratamiento antes y después de la triple terapia en EPOC: estudio poblacional en atención primaria en España" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 684 "Ancho" => 1333 "Tamanyo" => 123502 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airflow limitation and is a major cause of mortality and morbidity worldwide.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The aim of treatment of COPD is to reduce symptoms, decrease the frequency and severity of exacerbations and improve exercise tolerance and quality of life.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Pharmacological management is based on long-acting bronchodilators (LABD), either a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA) or both, and inhaled corticosteroids (ICS).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Current recommendations suggest to start with one LABD and step up to dual or triple therapy (TT) (ICS/LABA/LAMA), as necessary.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Therefore; TT is recommended only for patients with frequent exacerbations whose symptoms are not adequately controlled with either LABA/LAMA or ICS/LABA combination.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite these recommendations, TT is used extensively in current clinical practice, as has been reported in several studies around the world.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–9</span></a> Since TT is becoming increasingly important in clinical practice and over-prescription of inhaled medication is associated with increased costs and possible risk of side effects,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> it's important to understand the current situation of COPD patients with TT in real life and to evaluate the treatment pathways leading to TT. While some studies have been conducted to understand patient characteristics and factors related to TT use,<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,11,12</span></a> and the efficacy and tolerability of TT have been evaluated in several clinical trials,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13–15</span></a> there is limited “real world” information regarding pathways before and after initiation of TT.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objectives of this study were to characterize COPD patients who initiated TT and to describe treatment pathways before and after TT initiation in a population-based sample of patients with COPD in Primary Care.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study design</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a retrospective study with longitudinal follow-up using patient-level primary care data from 2011 to 2015. The data were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database, which contains anonymized computerized primary care medical records from 5.8 million people in Catalonia (Spain), which represents more than 80% of the total population.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> This database has been used and validated for epidemiological research in respiratory diseases.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,17</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patient selection</span><p id="par0025" class="elsevierStylePara elsevierViewall">We selected individuals older than 40 years, with at least one diagnosis of COPD (International Classification of Disease – 10th Edition [ICD-10] codes in <a class="elsevierStyleCrossRef" href="#sec0095">Appendix A</a>) and evidence of initiation of TT between January 1st, 2011 and December 31st, 2015. Initiation of TT was defined as having prescriptions for LAMA, LABA, and ICS with an overlap for ≥30 days. The date of prescription of the third component was defined as the start of TT or index date and this was the start of the data collection period for each patient. All patients were required to have at least 12-months of available medical record data prior to this index date (“pre-index”). Patients with any evidence of TT prescriptions during the pre-index period were excluded from study.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patient subgroups</span><p id="par0030" class="elsevierStylePara elsevierViewall">Patients were classified according to the Global Initiative for Chronic Obstructive lung Disease (GOLD) 2014 categories based on spirometry and exacerbation data as low risk (GOLD A/B) and high risk (GOLD C/D).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were also classified according to clinical phenotypes.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Those with two or more exacerbations during the year before initiation of triple therapy were classified as having a frequent exacerbator phenotype, patients with only one exacerbation were classified as infrequent exacerbators and the remaining COPD patients were considered non-exacerbators. Patients with a concomitant diagnosis of asthma were included in the asthma COPD overlap (ACO) phenotype.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Patients with available forced expiratory volume in one second (FEV1) results were classified into different levels of airflow limitation according to the most proximal FEV1 test results around index date (stage 1 mild, FEV<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>80% predicted, stage 2 moderate, 50%<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>FEV1<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>80% predicted; stage 3 severe, 30%<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>FEV1<<span class="elsevierStyleHsp" style=""></span>50% predicted; stage 4 very severe, FEV<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30% predicted).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Study measurements</span><p id="par0045" class="elsevierStylePara elsevierViewall">The following variables were obtained at baseline: demographic and clinical characteristics, including, age, sex, smoking history, comorbidities and episodes of pneumonia previous to the index date. Diagnostic spirometry, exacerbations, healthcare utilization and treatments received during the year before inclusion in the study were also collected. The blood analysis closest to the index date was selected to obtain the blood eosinophils values.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Exacerbation episodes were identified using outpatient visits with a diagnostic code indicative of a respiratory exacerbation, or receipt of corticosteroids and/or antibiotics used for treating exacerbations, in accordance with previously published algorithms.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,17</span></a> Exacerbations leading to hospitalizations or treated as part of inpatient care were not available in the data. To avoid misclassification and over-estimation of exacerbations, consecutive episodes with less than 21 days between prescriptions or general practitioner (GP) visits were considered as a single event.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Patients will be considered as having a step-down if they have discontinued on at least one of the three compounds LABA, LAMA, or ICS, defined as having no subsequent prescriptions during the 60 days from initiation of triple therapy, AND they had a subsequent prescription for at least one of the three compounds that is different than the one that was discontinued.</p><p id="par0060" class="elsevierStylePara elsevierViewall">A 60-day “gap” in subsequent prescriptions for all three components was considered as a discontinuation from TT. Patients who neither discontinue nor stepped down during follow-up were considered persistent on TT.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The study was approved by the Research and Ethics Committee of the IDIAP Jordi Gol Institute of Research In Primary Care (Barcelona, Spain). Since anonymised data were collected retrospectively, no informed consent was considered necessary.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">A descriptive analysis was performed with baseline sociodemographic, clinical characteristics and baseline treatments of patients included. Categorical variables were described using absolute frequencies and corresponding percentages. Continuous variables following a normal distribution were described using the mean and standard deviation (SD), while those that did not follow a normal distribution were describing using the median and interquartile range. Pathways and treatment following TT were presented as absolute frequencies and percentages.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Time to and probability of first event (step down or complete discontinuation) was described using restricted mean survival time (the average time-to-event in a restricted time-period) and using Kaplan–Meier analysis over 5 years of follow-up. The same analyses were performed according to GOLD severity and phenotype. All statistical analyses were performed using the statistical software package (SPSS version 20.0, IBM, Chicago, IL, USA).</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall">During the study period, a total of 197,189 patients with recorded diagnosis of COPD were identified; of whom 34,018 (17.2%) initiated TT and constituted the study population. Among these patients, 8.6% initiated TT prior to COPD diagnosis, 5.3% at COPD diagnosis and 86.1% after COPD diagnosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Baseline characteristics at initiation of triple therapy</span><p id="par0085" class="elsevierStylePara elsevierViewall">In total, 26,619 (78.2%) patients were men. Mean age was 72.4 years (SD: 10.4) and mean duration of disease was 5.9 years (SD: 5.8). Up to 92% of patients had blood analysis performed during the year before TT initiation and mean eosinophil count was 247.6<span class="elsevierStyleHsp" style=""></span>cells/μl (SD: 162.6); in contrast, only 35.3% of patients had spirometry and mean FEV1 (% predicted) was 51.9% (SD: 19%).</p><p id="par0090" class="elsevierStylePara elsevierViewall">The majority of patients who initiated TT (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>23,867, 70.1%) were GOLD A/B. Regarding phenotype, most patients were non-exacerbators 18,453 (54.2%) followed by infrequent exacerbators 9931 (29.2%) and the remaining 5634 patients (16.5%) were frequent exacerbators. Of all patients, 1923 (5.6%) were classified as having ACO (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The most frequent respiratory-related comorbidities were respiratory infections (20.2%), pneumonia (10.3%) and bronchiectasis (8.1%). The most frequent non-respiratory comorbidities were hypertension (59.4%), hypercholesterolemia (44.6%), obesity (26.6%) and diabetes mellitus (25.5%). The main characteristics of the population are described in detail in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Treatment used before triple therapy</span><p id="par0100" class="elsevierStylePara elsevierViewall">Drugs more frequently used prior to initiation of TT were LAMA, LABA/ICS and ICS (22.5%, 15.2% and 8.2%, respectively).</p><p id="par0105" class="elsevierStylePara elsevierViewall">Use of LABA/ICS before TT was most frequent among patients with ACO (44.3%), frequent exacerbators (36.9%) and GOLD C/D (34.3%) patients; while the use of LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICS at any time in the previous year, but overlapping less than 30 days (not fulfilling the definition of TT) was most frequent in frequent exacerbators (17.9%) and GOLD C/D (16.4%) patients. LABA/ICS was prescribed to 31.6% of infrequent exacerbators and 27.4% of non-exacerbators, whilst LABA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>LAMA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ICS were prescribed to 14.1%, and 11.7%, respectively. (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Pathways following triple therapy initiation</span><p id="par0110" class="elsevierStylePara elsevierViewall">A total of 21,261 (62.5%) patients continued receiving TT throughout follow-up. However, 11,666 patients (34.3%) stepped down from TT and 1091 patients (3.2%) discontinued TT at any time during follow-up. Distribution of pathways following TT initiation was similar between subgroups (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Time to step down or discontinuation</span><p id="par0115" class="elsevierStylePara elsevierViewall">Over 5 years of follow-up, 11,666 (34.3%) patients stepped down from TT. Of them, 7710 (66.1%) did so within one year of TT initiation, and 9984 (85.6%) and 11,059 (94.8%) after two and three years, respectively. Patterns of step down were similar across subgroups (data not shown). The restricted mean time to step down following TT initiation was 38.9 months (95%CI, 51.3–57.9) and was similar across GOLD subgroups. However, among phenotypes, frequent exacerbators stepped down around 3 months earlier (36.2 months) than non-exacerbators (39.6 months) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). On the other hand, 1091 (3.2%) patients presented complete discontinuation with a restricted mean time to discontinuation of 58.4 months (95%CI, NA), similar across subgroups (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Kaplan Meier analysis showed that patients starting TT had a 50% probability of step down at 5 years of follow-up. Higher proportions of step downs were observed in frequent exacerbators and patients with ACO; however, observed proportions were similar across GOLD subgroups (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Probability of TT discontinuation within 5 years was about 6%, with higher proportion in milder patients (GOLD A/B, non-exacerbators and non-frequent exacerbators) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Treatment following triple therapy</span><p id="par0125" class="elsevierStylePara elsevierViewall">The COPD medications more frequently prescribed during the next 30 days after stepping down from TT were LABA/ICS (42.4%), LAMA (22.4%) and LABA/LAMA (18.9%). No significant differences were seen between subgroups (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0130" class="elsevierStylePara elsevierViewall">The current study provides a description of the clinical profile of patients with COPD who initiated treatment with TT and treatment pathways prior and following TT initiation in real-life clinical practice. We observed that patients who initiate TT often receive ICS containing regimens as prior treatment and without having experienced exacerbations in the year prior, suggesting that less severe patients are receiving TT, in contrast to treatment recommendations. Treatment with TT tends to remain persistent irrespective of the severity of the disease and the level of risk. Step down following TT is more likely in severe patients, especially during the first year.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Prescription of TT for COPD patients is common in current clinical practice<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,20–22</span></a> and it's increasing in recent years. A recent study performed in UK using real world data showed an increase of incident TT prescriptions from less than 1% in 2001 to 26% in 2016, and an increase in prevalent TT prescription from 1% to 41% in the same period.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A similar increase was observed in Spain, where a previous epidemiological study by Barrecheguren et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> showed that 12% of newly diagnosed COPD patients initiated TT during 2006–2012, which increased to 17% of incident TT during 2011–2015 in our study. Similarly, our study found 18% of patients eligible to be in the study to be receiving TT. Although this percentage is still lower than that observed in other international studies,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7,21,22</span></a> findings support a consistent trend of increasing TT prescription in Primary Care.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Guidelines published during the study period recommended the use of TT in patients with severe disease, frequent exacerbations and persistent symptoms who were not adequately controlled with LABA/LAMA or ICS/LABA combination.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> These recommendations are supported by accumulated evidence from clinical trials showing the benefits of TT compared with dual or monotherapy in more severe patients with exacerbations.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> However, real life data indicate that TT prescription patterns often differ from the current recommendations and there has been a reported overuse of TT in different levels of health care, from Primary Care to hospital-based respiratory clinics.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5,7,20–22</span></a> Interestingly, the majority of patients who initiated TT in our study population were classified as GOLD A/B, in whom TT is not recommended. This finding is not unique to Spain, as previous works performed in the UK,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> the US,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> central and Eastern Europe,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Latin America<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> and Japan<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> have also shown the over-prescription of TT in patients who are not frequent exacerbators and belong to the GOLD groups A or B. These findings suggest that primary care physicians may rely more on symptoms than exacerbations for their decisions to step up pharmacologic therapy. This hypothesis is supported by several studies that reported progression to TT with no prior exacerbations history,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7,11</span></a> including a recent study by Landis et al.,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> which found that dyspnea was the main driver for therapy changes in COPD patients in Primary Care. However, there is some evidence for the use of TT irrespective of reported exacerbation history. For example, subgroup analyses from the KRONOS trial suggest a benefit of TT over dual therapy even in patients with no exacerbation in the past year.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The Spanish COPD guidelines<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> at the time of the study recommended the use of ICS in patients identified as ACO and/or frequent exacerbators. It is unlikely that the high use of TT was due to a high prevalence of ACO, because only 5.6% of patients were identified as ACO and the prevalence of high blood eosinophil counts was not high enough to justify the use of TT. It is of note, however, that the mean value of blood eosinophil concentrations for our population were relatively high at 247<span class="elsevierStyleHsp" style=""></span>cell/μl. This is similar to a previous study in Spain reporting a mean value of 254<span class="elsevierStyleHsp" style=""></span>cell/μl in a population of 57,000 unselected patients with COPD at all levels of severity.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Recently, Kolsum et al.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> obtained a mean eosinophil count of 210<span class="elsevierStyleHsp" style=""></span>cell/μl in patients with COPD, which was significantly higher than counts observed in smokers without COPD and health controls.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Our results highlight prescription of ICS-combined regimens and a later escalation to TT, irrespective of exacerbation frequency.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,11,20,26,30–33</span></a> These findings may indicate however, that such use may be warranted for some patients and may be reflective of underreporting of exacerbations or control of exacerbations with ICS therapy. However, if used when not appropriate, prior therapy with ICS-containing regimens could result in limited clinical benefits. Consequently, GPs may decide to escalate treatment to TT instead of changing to a non ICS-containing regimen to control disease.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Interestingly, around 20% of patients who initiated TT had no history of previous COPD medication. A similar percentage has been observed in other studies<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,34</span></a> and indicates again a deviation from treatment recommendations.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">We observed that the probability of de-escalation following TT within 5 years is around 50%, but particularly in patients with more severe disease (frequent exacerbators and patients with ACOS) and during the first year. This unexpected result may be due to lack of efficacy despite receiving TT,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> or on the contrary, due to an effective disease stability achieved after TT.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35–37</span></a> In addition, we cannot rule out that more frequent contacts of severe patients with the healthcare providers may increase the probability of treatment changes, including de-escalation from TT. Unfortunately, we do not have enough clinical information to address the reason for de-escalation; long term follow up and complete sequencing of treatments after TT initiation may be warranted to best investigate reasons for change in treatment patterns.</p><p id="par0165" class="elsevierStylePara elsevierViewall">In a number of cases, step down consisted of discontinuation of a LABD with persistence of the ICS component. This is consistent with other studies<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> but contrasts clinical trials demonstrating that ICS can be safely discontinued in some patients with stable COPD, particularly in non-exacerbators with low blood eosinophil counts.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> We observed 6% probability of complete discontinuation of TT within 5 years, especially in less severe patients,<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> which is not consistent with current recommendations that suggest LABD treatment in symptomatic COPD.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The current study has some limitations; as in most real word data studies, caution should be taken when interpreting results relating to choice of therapy as the full context of the decision is not recorded. Full categorization of COPD patients was not possible, as symptoms data, including CAT scores and mMRC are not available in SIDIAP and information on lung function is limited; therefore, GOLD categorisation was only possible in two groups A/B or C/D. Although we used a validated algorithm to identify exacerbations, the risk of underreporting still exists and underreporting of exacerbations by patients is also is well documented in the literature. In addition, exacerbations leading to hospitalization or those treated directly by respiratory specialists were not available; however, these episodes are less frequent in and the majority of these episodes can be captured based on prescriptions following the exacerbation episode. Last, exacerbations were only considered over a 12-month period, longer-term monitoring could be useful to further understand exacerbation frequency and treatment patterns. In any case, if underreporting exists, it should affect equally to all subgroups and should not affect significantly the conclusions of the study. Since new evidence on efficacy and safety of inhaled medication is available and guidelines have been modified, it would be relevant to repeat the study to see if there has been any change in the trends observed.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0175" class="elsevierStylePara elsevierViewall">In conclusion, our results suggest that there is extensive use of TT in primary care, and that the use of TT is not consistent with guideline recommendations. Most patients initiating treatment with TT continue on the same treatment over time regardless of severity of disease. Step down was most frequent in severe patients, while discontinuation was most common among patients with less severe disease. The findings suggest that further research into the drivers of TT prescription in clinical practice would be beneficial.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Authors’ contributions</span><p id="par0180" class="elsevierStylePara elsevierViewall">DL, ND, AB conceived and designed the study. MMo and IS coordinated statistical analyses. MM and MMo wrote manuscript. All authors contributed to study design and analysis, drafting, reviewing, and critically revising the paper, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, pH Pharma, Novartis, Sanofi and Grifols and research grants from GlaxoSmithKline and Grifols. Miriam Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GSK and consulting fees from GSK and Novartis. D. Lambrelli, N. Dhalwani and A. Booth are employees of Evidera. The authors confirm there are no other conflicts of interest to report.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1521797" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres1521796" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1379909" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres1521795" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusión" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1379910" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patient selection" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Patient subgroups" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Study measurements" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 7 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Baseline characteristics at initiation of triple therapy" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Treatment used before triple therapy" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Pathways following triple therapy initiation" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Time to step down or discontinuation" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "Treatment following triple therapy" ] ] ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Authors’ contributions" ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack534483" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-05-19" "fechaAceptado" => "2020-07-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1379909" "palabras" => array:4 [ 0 => "COPD" 1 => "Triple therapy" 2 => "Treatment" 3 => "Primary care" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1379910" "palabras" => array:4 [ 0 => "EPOC" 1 => "Triple terapia" 2 => "Tratamiento" 3 => "Atención primaria" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Background</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Recent data from real world clinical practices on the use of Triple Therapy (TT) in patients with COPD are scarce.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Observational population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical records database in Catalonia, covering 80% of the general population. The aims were to characterize COPD patients who initiated TT and to describe treatment pathways before and after TT initiation. Time to and probability of step down or complete discontinuation of TT was described using restricted mean survival time and Kaplan–Meier analysis.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 34,018 COPD patients initiated TT during the study period. Of them, 23,867 (70.1%) were GOLD A/B. 18,453 (54.2%) were non-exacerbators, 9931 (29.2%) infrequent exacerbators, 5634 (16.5%) frequent exacerbators and 1923 (5.6%) had asthma-COPD overlap. Drugs most frequently used prior to initiation of TT were long-acting antimuscarinics (22.5%) and combination of long-acting beta2 agonists/inhaled corticosteroids (15.2%). A total of 11,666 (34.3%) stepped down and 1091 (3.2%) discontinued TT during follow-up. Step down following TT was more likely in patients with severe COPD, especially during the first year; however, discontinuation was more common among patients with mild COPD.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Most patients initiating treatment with TT were non exacerbators and continued on the same treatment over time regardless severity of disease. Stepping down was more frequent in severe patients, while discontinuation was more common among mild patients. Overall, it appears that TT is extensively used in primary care for treatment of patients with COPD.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se dispone de pocos datos recientes de práctica clínica en el mundo real sobre el uso de la triple terapia (TT) en pacientes con EPOC.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional de base poblacional con seguimiento longitudinal en pacientes con EPOC identificados en una base de datos de historiales médicos electrónicos de atención primaria en Cataluña, que abarca el 80% de la población general. Los objetivos fueron caracterizar a los pacientes con EPOC que iniciaron la TT, y describir las vías de tratamiento antes y después del inicio de la TT. Se describió el tiempo y la probabilidad de desescalada o la suspensión completa de la TT utilizando el tiempo de supervivencia medio restringido y el análisis de Kaplan-Meier.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Un total de 34.018 pacientes con EPOC iniciaron TT durante el período de estudio. De ellos, 23.867 (70,1%) eran GOLD A/B, 18.453 (54,2%) eran no exacerbadores, 9.931 (29,2%) exacerbadores infrecuentes, 5.634 (16,5%) exacerbadores frecuentes y 1.923 (5,6%) presentaban superposición asma-EPOC. Los fármacos que se usaron con mayor frecuencia antes del inicio de la TT fueron los antimuscarínicos de acción prolongada (22,5%), y la combinación de agonistas beta2 de acción prolongada/corticosteroides inhalados (15,2%). Un total de 11.666 pacientes (34,3%) desescalaron la TT y 1.091 (3,2%) suspendieron el tratamiento durante el seguimiento. La desescalada después de la TT fue más probable en pacientes con EPOC grave, especialmente durante el primer año; sin embargo, la suspensión fue más común en pacientes con EPOC leve.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusión</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La mayoría de los pacientes que iniciaron el tratamiento con la TT eran no exacerbadores y continuaron con el mismo tratamiento, independientemente de la gravedad de la enfermedad. La desescalada fue más frecuente en pacientes graves, mientras que la suspensión fue más común entre los pacientes leves. En general, parece que la TT se utiliza ampliamente en el nivel de atención primaria para el tratamiento de pacientes con EPOC.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusión" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0205" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0095" ] ] ] ] "multimedia" => array:10 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2176 "Ancho" => 2423 "Tamanyo" => 248856 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Flow-chart diagram of the study population.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1199 "Ancho" => 2179 "Tamanyo" => 110064 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Distribution of pathways following triple therapy in overall and by subgroups of interest.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1955 "Ancho" => 2453 "Tamanyo" => 179775 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">A. Kaplan Meier curves to show rates of step-down following triple therapy at 5 years post index date. (A) by phenotype; (B) by GOLD groups AB/CD.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1894 "Ancho" => 2513 "Tamanyo" => 179399 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Kaplan–Meier curves to show rates of discontinuation following triple therapy at 5 years post index date. (A) by phenotype; (B) by GOLD groups AB/CD.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">The data are <span class="elsevierStyleItalic">n</span> (%), unless otherwise indicated. SD, standard deviation; ACO, asthma COPD overlap; FEV1, forced expiratory volume in 1s; GOLD, global initiative for obstructive chronic pulmonary disease.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incident triple therapy cohort<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>34,018 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GOLD A/B (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>23,867) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">GOLD C/D (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10,151) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ACO (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1923) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Frequent exacerbators (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5634) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Infrequent exacerbators (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp"