Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow restriction and respiratory symptoms such as dyspnoea, cough, and sputum production.¹ While COPD is a mainly chronic disease, some patients may experience COPD exacerbation, during which acute worsening of symptoms occurs.¹ Although the risk of severe cardiovascular (CV) events has been shown to increase following severe exacerbations of COPD that required hospitalization, the durations of increased risk as well as the effect of moderate exacerbations treated in an outpatient setting an outpatient basis are unclear.^1,2 The EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV)  study group thus conducted a multi-database, retrospective observational cohort study which aims to quantify the risk of a severe CV event or death within different periods following a moderate or severe COPD exacerbation.^1,2

The study included patients with COPD in secondary databases in Canada, Germany, the Netherlands, and Spain between 2014-2018.²  Follow-up was started upon the first identified COPD code until the patient experienced a composite outcome [all-cause death, hospitalization for decompensated heart failure (HF), acute coronary syndrome (ACS), arrhythmias or cerebral ischemia], was lost to follow-up,  or until 31 December 2019.² Time-dependent Cox models were utilized to compare the outcome risk incrementally over 12 months following a COPD exacerbation (exposed) to periods outside an exacerbation (unexposed).²

A total of 142,787 patients (median age: 68 years; 51.7% men) from Canada, 126,795 patients (median age: 67 years; 60.0% men) from Germany, 24,393 patients (median age: 68 years; 78.²% men) from Spain, and 8,020 patients (median age: 65 years; 52.7% men) from the Netherlands were included in the evaluation.² Additionally, the majority of these patients did not experience an exacerbation in the previous 12 months before the analysis started.²

The median duration of follow-up was 36 months in Germany, the Netherlands and Spain, and 58 months in Canada.² During this period, the researchers observed ≥1 moderate exacerbation among 26.6% of the Canadian cohort, 29.7% of the German cohort, 58.6% of the Spanish cohort, and 23.3% of the Netherlands cohort.² The proportion of patients who had ≥1 severe exacerbation was  similar to patients who had moderate exacerbations in Canada (30.2%)  and Germany (27.0%), but lower in Spain (9.5%) and the  Netherlands (9.3%).² The proportion of patients who experienced a CV event or all-cause death during the study follow-up was highest in Germany (38.6%), followed by Spain (35.8%), Canada (30.5%) and the Netherlands (13.7%).²

The researchers found that having a moderate exacerbation of COPD increased the risk of CV events or death for at least 30 days after onset, however, this effect was reduced during the 31-180 days  and 181-365 days exposed period (Canada HR=0.94; 95% CI: 0.87-1.00, Germany HR=0.91; 95% CI: 0.86-0.96, Spain HR=0.71;  95% CI: 0.61-0.84, Netherlands HR=1.26; 95% CI: 0.93-1.72).²

Moreover, patients who experienced a severe exacerbation of COPD had significantly higher risk of developing a CV event or death for the whole observation period.² The increased risk persisted within the 181-365 days exposed period in all included countries (Canada HR=1.47; 95% CI: 1.40-1.55, Germany HR=1.17; 95% CI: 1.11-1.23, Spain HR=3.10; 95% CI: 2.77-3.46, Netherlands HR=1.61; 95% CI: 1.01-2.56), although this was reduced compared to the initial 1-7 day  period (Canada HR=24.88; 95% CI: 23.75-26.07, Germany HR=15.84; 95% CI: 15.26-16.45, Spain HR=24.22; 95% CI: 21.77-26.96, Netherlands HR=48.57; 95% CI: 36.88-63.96).²

In conclusion, the results of this study show that patients experience a markedly elevated risk of a severe CV event or death which persisted for a minimum of 30 days following a moderate exacerbation, and for at least a year following a severe exacerbation.² Importantly, these results were consistent in a large study population across various countries and healthcare systems.² The study also highlighted the potential mechanisms underlying the association between COPD exacerbation and a subsequent CV event, such as increased hypoxemia, cardiac stress, risk of plaque rupture, or decompensated HF.¹ Considering the substantial impact of COPD exacerbations beyond the respiratory system, it is crucial to develop more effective strategies to reduce the risk of exacerbations.²