Kardos, PeterWorsley, SallySingh, DaveRoman-Rodriguez, MiguelNewby, David EMullerova, Hana2024-07-092024-07-092016Kardos P, Worsley S, Singh D, Roman-Rodriguez M, Newby DE, Mullerova H. Randomized controlled trials and real-world observational studies in evaluating cardiovascular safety of inhaled bronchodilator therapy in COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2885-2895.1178-2005http://hdl.handle.net/20.500.13003/17226http://hdl.handle.net/20.500.12105/20235Long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Although the efficacy of LAMAs and LABAs has been well established through randomized controlled trials (RCTs), questions remain regarding their cardiovascular (CV) safety. Furthermore, while the safety of LAMA and LABA monotherapy has been extensively studied, data are lacking for LAMA/LABA combination therapy, and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically designed to assess this. Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities. However, severe CV and other comorbidities are often exclusion criteria for RCTs, contributing to a lack in external validity and generalizability. Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs. We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies, and explore the advantages and limitations of data derived from each study type. We also describe an ongoing prospective, observational, comparative post-authorization safety study of a LAMA/LABA combination therapy (umeclidinium/vilanterol) and LAMA monotherapy (umeclidinium) versus tiotropium, with a focus on the relative merits of the study design.enghttp://creativecommons.org/licenses/by-nc/4.0/CardiovascularCerebrovascularReal-world observational studySafetyUmeclidiniumVilanterolCardiovascular DiseasesRandomized Controlled Trials as TopicChlorobenzenesDrug CombinationsRisk AssessmentPulmonary Disease, Chronic ObstructiveHumansBenzyl AlcoholsBronchodilator AgentsPatient SafetyLungResearch DesignProspective StudiesTime FactorsMuscarinic AntagonistsQuinuclidinesRisk FactorsEvidence-Based MedicinePatient SelectionComorbidityresearch articleAttribution-NonCommercial 4.0 International27932872112885-289510.2147/COPD.S118867International Journal of Chronic Obstructive Pulmonary Diseaseopen accessSelección de PacienteComorbilidadMedicina Basada en la EvidenciaSeguridad del PacienteFactores de TiempoPulmónAntagonistas MuscarínicosAlcoholes BencílicosEnfermedad Pulmonar Obstructiva CrónicaQuinuclidinasFactores de RiesgoBroncodilatadoresCombinación de MedicamentosHumanosProyectos de InvestigaciónEstudios ProspectivosMedición de RiesgoClorobencenosEnfermedades CardiovascularesEnsayos Clínicos Controlados Aleatorios como Asunto2-s2.0-85000580117L613447237