The sustained increase of cardiovascular risk following COPD exacerbations: meta-analyses of the EXACOS-CV studies

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.

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.

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.

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.