Clarithromycin Versus Azithromycin for Community-Acquired Pneumonia and the Risk of Major Adverse Cardiovascular Events: A Multicentre Cohort Study Using Data From Canada and Denmark.

Background: Studies suggest that clarithromycin is associated with an increased risk of major adverse cardiovascular events (MACE) among adults with coronary artery disease. However, data comparing clarithromycin to other macrolides, such as azithromycin, in a broader population are lacking.

Methods: A multicenter study was conducted in 33 hospitals in Ontario, Canada, and Copenhagen, Denmark, using the Target Trial framework. Adults hospitalized with community-acquired pneumonia (CAP) who received either clarithromycin or azithromycin were included. The primary outcome was MACE, defined as the one-year risk of nonfatal myocardial infarction, nonfatal stroke, or all-cause mortality. Propensity score matching and Cox proportional hazards models were used for analysis.

Results: In Ontario, we identified 23 081 patients with CAP, and 11 164 received oral macrolides. After propensity score matching, the primary outcome occurred in 7.8% of clarithromycin patients and 9.1% of azithromycin patients (HR 0.85, 95% CI 0.60-1.21). In Copenhagen, there were 11 280 patients with CAP and 3924 received oral macrolides. After propensity score matching, 19% of clarithromycin patients and 12% of azithromycin patients experienced the primary outcome for oral macrolides (HR 1.7, 95% CI 1.2-2.4, p = 0.002). Meta-analysis of the point estimate from each country provided an overall HR of 1.21 (95% CI 0.61-2.39). For intravenous macrolides in Copenhagen, the HR was 1.15 (95% CI 1.0-1.3, p = 0.007) for clarithromycin compared to azithromycin.

Conclusion: This study did not consistently observe an increased risk of cardiovascular events with clarithromycin among adults hospitalized with CAP. However, the observational nature of the study may introduce selection bias and unmeasured confounding.