Risk of major cardiovascular events and bleeding in atrial fibrillation patients with chronic obstructive pulmonary disease treated with low dose azithromycin prophylaxis

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events in patients with atrial fibrillation (AF). Low Dose Azithromycin Prophylaxis (LDAP) is associated with improved outcomes in people suffering frequent exacerbations of COPD, but the widespread use of macrolides in patients with underlying cardiovascular disease has been debated due to safety concerns. Aims and Objectives To investigate the safety and efficacy of LDAP in AF patients with COPD in a large global federated dataset. Methods We conducted a retrospective cohort study within the global TriNetX Platform, including AF patients with COPD exacerbations. Risks for all-cause death, major adverse cardiovascular events (MACE: acute coronary syndrome, thromboembolic events, severe ventricular arrhythmias, and heart failure), intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding were recorded up to 30 days post-COPD exacerbations and compared between LDAP users (at least 3 months use and using LDAP at index) and an active control group (non-Azithromycin users receiving inhaled corticosteroids (ICS)). Cox regression analyses compared outcomes between groups after propensity-score-matching (PSM) for cardiovascular risk factors. Results We identified 2791 LDAP users with COPD and AF (mean age 71.5±10.6 years, 48.9% female), and 61054 controls. Before PSM, LDAP users showed a lower prevalence of cardiovascular risk factors and were less likely to be prescribed oral anticoagulation (68.1% vs 76.1%, p<0.001). After PSM no significant baseline differences were found between two groups. After COPD exacerbation, LDAP users were associated with a lower 30-day risk of all-cause death (HR: 0.72, 95%CI 0.60-0.97), MACE (HR 0.72, 95%CI 0.57-0.90), ICH (0.48, 95%CI 0.27-0.88) and GI bleeding (HR 0.69,95%CI 0.46-0.89) compared to the conventional treatment with ICS. Analysing the different time frames, the lower risk of thrombotic events was observed during the second week after COPD exacerbation while the magnitude of the bleeding risk reduction was more evident in the first 7 days (Figure 1). Conclusion LDAP use is associated with a lower risk of all-cause death, MACE and bleeding in AF patients with COPD. Further studies are needed to investigate the possible role of LDAP as part of the integrated care management of AF patients with COPD.