Introduction: Patients with chronic obstructive pulmonary disease (COPD) frequently have cardiovascular comorbidities, increasing the risk of hospitalised COPD exacerbations (H-ECOPDs) or death. This pragmatic study examined the effects of adding an inhaled corticosteroid (ICS) to long-acting bronchodilator(s) (LABDs) in patients with COPD and cardiac comorbidities who had a recent H-ECOPD., Methods: Patients >60 years of age with COPD and ≥1 cardiac comorbidity, within 6 months after discharge following an H-ECOPD, were randomised to receive LABD(s) with or without ICS, and were followed for 1 year. The primary outcome was the time to first rehospitalisation and/or all-cause death., Results: The planned number of patients was not recruited (803/1032), limiting the strength of the conclusions. In the intention-to-treat population, 89/403 patients (22.1 %) were rehospitalised or died in the LABD group (probability 0.257 [95 % confidence interval 0.206, 0.318]), vs 85/400 (21.3 %) in the LABD+ICS group (0.249 [0.198, 0.310]), with no difference between groups in time-to-event (hazard ratio 1.116 [0.827, 1.504]; p = 0.473). All-cause and cardiovascular mortality were lower in patients receiving LABD(s)+ICS, with relative reductions of 19.7 % and 27.4 %, respectively (9.8 % vs 12.2 % and 4.5 % vs 6.2 %), although the groups were not formally statistically compared for these endpoints. Fewer patients had adverse events in the LABD+ICS group (43.0 % vs 50.4 %; p = 0.013), with 4.9 % vs 5.4 % reporting pneumonia adverse events., Conclusions: Results suggest addition of ICS to LABDs did not reduce the time-to-combined rehospitalisation/death, although it decreased all-cause and cardiovascular mortality. ICS use was not associated with an increased risk of adverse events, particularly pneumonia., Competing Interests: Declaration of competing interest In addition to the medical writing support disclosed below, the authors have the following conflicts of interest. Alberto Papi reports grants to his institution from Chiesi, AstraZeneca, GlaxoSmithKline and Sanofi, consulting fees from Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, Moderna, and Roche, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, AstraZeneca, GlaxoSmithKline, Menarini, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion, Sanofi, and Regeneron, and participation on advisory boards for Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, and Moderna. All are outside the scope of the current manuscript. Giacomo Forini has no other conflicts to disclose. Mauro Maniscalco declares grants or contracts (with payments to Istituti Clinici Scientifici Maugeri IRCCS) from GlaxoSmithKline and AstraZeneca, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline, AstraZeneca, and Chiesi. All are outside the scope of the current manuscript. Elena Bargagli has no other conflicts to disclose. Claudia Crimi received honoraria for lectures from Fisher & Paykel, ResMed, AstraZeneca, Sanofi, GlaxoSmithKline, and Vitalaire. All are outside the scope of the current manuscript. Pierachille Santus declares research grants from AstraZeneca, Edmondpharma, GlaxoSmithKline, and Novartis (payments were made to the Department of Biomedical and Clinical Sciences of University of Milan), consulting fees from GlaxoSmithKline, Sanofi, Edmondpharma, Dompè, Valeas, and Neopharmed, and honoraria for lectures from AstraZeneca, Sanofi, GlaxoSmithKline, Berlin Chemie, Edmondpharma, and Zambon Brasil. All are outside the scope of the current manuscript. Antonio Molino has no other conflicts to disclose. Valeria Bandiera is an employee of Alira Health SrI, which received funding from the Università degli Studi di Ferrara to provide biometrics services to the study. Federico Baraldi received a short-term research fellowship from the European Respiratory Society, outside the scope of the current manuscript Silvestro Ennio D'Anna has no other conflicts to disclose. Mauro Carone received honoraria as speaker from GlaxoSmithKline and AstraZeneca, and honoraria for participation in speaker bureaus from Boehringer Ingelheim, support for attending meetings and travel from the Associazione Italiana Pneumologi Ospedalieri – Italian Thoracic Society (AIPO-ITS/ETS), and an unpaid role as the National President of the AIPO-ITS/ETS. All are outside the scope of the current manuscript. Maurizio Marvisi has no other conflicts to disclose. Corrado Pelaia received honoraria for lectures from AstraZeneca, GlaxoSmithKline, and Sanofi, all outside the scope of the current manuscript. Giulia Scioscia has no other conflicts to disclose. Vincenzo Patella has no other conflicts to disclose. Maria Aliani has no other conflicts to disclose. Leonardo M Fabbri received consulting fees from Alfasigma, AstraZeneca, Chiesi, GlaxoSmithKline, ICON, Menarini, Novartis, and Verona Pharma, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, GlaxoSmithKline, Glenmark, Lusofama, and Novartis, support for attending meetings and/or travel from the Italian Society of Allergy, Asthma and Clinical Immunology and the Menarini Foundation, and participated in a data safety monitoring board or advisory board for Novartis, Chiesi, and ICON. All are outside the scope of the current manuscript., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)