Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin and Amoxicillin in Primary and Secondary Care.

Background

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition where many patients are given antibiotics like amoxicillin and macrolides (clarithromycin, azithromycin, roxithromycin) for bacterial infections. Recent concerns about clarithromycin's potential link to cardiovascular events have arisen, despite its effectiveness against respiratory pathogens. This study aims to compare the cardiovascular risk of macrolide antibiotics versus amoxicillin in suspected COPD patients. Method: We used the Danish National Health Service Prescription Database (DNHSP) to identify COPD patients and their use of antibiotics. The included COPD patients were divided into four groups: amoxicillin users, roxithromycin users, clarithromycin users and azithromycin users. Data from multiple registries were merged to track hospitalizations, causes of death, and major adverse cardiovascular events (MACEs) as the primary endpoint. Patients were followed for a 3-year period. We applied adjusted Cox regression and sensitivity analyses with IPTW and IPCW to address confounders and censoring.

Results

Our study involved 45,869 patients who were prescribed a long-acting muscarinic antagonist, over the age of 40 years old and who received one of the following antibiotics: amoxicillin, azithromycin, clarithromycin, or roxithromycin. No increased risk of MACEs was observed in macrolide-treated patients compared to those treated with amoxicillin (azithromycin: HR 0.97: 95% CI 0.83-1.13 p = 0.69, clarithromycin: HR 1.06 95% CI 0.87-1.28 p = 0.57, roxithromycin: HR 1.04 95% CI 0.91-1.18 p = 0.60), as confirmed by the sensitivity analysis (azithromycin: HR 0.95 95% CI 0.82-1.11 p = 0.52, clarithromycin: HR 1.05 95% CI 0.87-1.27 p = 0.60, roxithromycin: HR 1.05 95% CI 0.92-1.19 p = 0.48). Similarly, hazard ratios for all-cause mortality and cardiovascular death among the antibiotic groups showed no significant statistical differences.

Conclusions

These findings suggest that there is no difference in the risk of MACEs, all-cause mortality, or cardiovascular death between the amoxicillin group and the macrolide group in a large and unselected population of COPD patients.