Does azithromycin modulate cardiovascular risk following acute pulmonary exacerbations of chronic obstructive pulmonary disease?

<b>Introduction:</b> Long-term azithromycin (AZM) reduces inflammation and acute exacerbations of COPD (AECOPD), key predictors of cardiovascular events. We were therefore interested to understand whether AZM modulates cardiovascular risk in AECOPD. Aims and Objective: Investigate cardiovascular outcomes following AECOPD in AZM users and non-users. <b>Methods:</b> We conducted a retrospective cohort study within the global TriNetX Platform. Major adverse cardiovascular events (MACE: acute coronary, stroke, arrythmia or heart failure) were recorded up to 30 days post-AECOPD and compared between AZM users (at least 3 months use and using at index) and non-users. Cardiac risk factor propensity-matched logistic regression analyses compared MACE between groups. <b>Results:</b> We identified 13,564 AZM users and 341,448 non-users. MACE was reduced in AZM users at day 30 (Hazard Ratio [95% CI] 0.90 [0.86 to 0.94], p&lt;0.001). Reduced all-cause mortality (HR 0.71 [0.59 to 0.85], p&lt;0.001), myocardial infarction (HR 0.85 [0.76 to 0.96], p=0.006), and heart failure (HR 0.91 [0.87 to 0.97], p=0.002) were the major drivers of improved outcomes. No increased risk of arrythmia and no difference in ischaemic stroke were observed. Sub-group analyses generally showed greatest effects in the first week compared to weeks 2-4. <b>Conclusion:</b> We found long-term macrolide use was associated with reduced cardiovascular risk up to 30 days after an AECOPD and effects were most pronounced in the first week, previously shown to the period of highest cardiovascular risk. More work is needed to understand the role of AZM in cardiovascular disease risk modulation in people with chronic lung disease.