The sustained increase of cardiovascular risk following COPD exacerbations: meta-analyses of the EXACOS-CV studies
Clémentine Nordon, Sami O. Simons, Jonathan Marshall, Hana Müllerová, Michael Pollack, Camilla Bengtsson, Fabian Hoti, Muriel Lobier, Aaro Salosensaari, Ana C. Santos, Claus Vogelmeier, Kirsty Rhodes
Abstract
Background The EXAcerbations of COPD and their OutcomeS on CardioVascular disease (EXACOS-CV) multi-database studies have consistently shown an increased risk of serious cardiovascular event following COPD exacerbations, but with some risk temporality variations. EXACOS-CV results were meta-analysed to increase their generalisability and improve precision. Methods Studies conducted in Canada, the United States, Germany, the Netherlands, Spain, Italy, Japan and England were meta-analysed, amounting to 1 030 875 individuals. Generally, each study included individuals aged ≥40 years with a COPD diagnosis in 2014–2019; primary outcome was the composite of non-fatal acute coronary syndrome, decompensated heart failure, ischaemic stroke, arrhythmias and all-cause death. Pooled hazard ratios (HR p ) of risks in post-exacerbation periods ( versus periods outside exacerbations) were obtained through random effects meta-analysis. Results Time periods following an exacerbation (any severity) were associated with increased and sustained risks of the composite outcome: HR p 10.22 (95% CI 5.34–19.57) in days 1–7 and HR p 1.24 (95% CI 1.09–1.40) in days 181–365. Risks were elevated for 6 months (HR p 1.25, 95% CI 1.01–1.55 in days 31–180) and 1 year (HR p 1.48, 95% CI 1.11–1.96 in days 181–365) following a moderate or a severe exacerbation, respectively. In newly diagnosed individuals, risks were increased until days 31–180: HR p 1.66 (95% CI 1.14–2.42) and HR p 1.61 (95% CI 1.28–2.02) following the first and the second post-diagnosis exacerbation, respectively. Conclusion Risk of severe cardiovascular events is sustainably increased following an exacerbation of COPD, even early and moderate ones. Cardiopulmonary risk reduction should be a global core target of COPD management.