Does macrolide use confer risk of out-of-hospital cardiac arrest compared with penicillin V? A Danish national case-crossover and case–time–control study

INTRODUCTION AND OBJECTIVES: Macrolides have been associated with proarrhythmic properties, but the evidence is conflicting. We evaluated the risk of out-of-hospital cardiac arrest (OHCA) associated with specific macrolides in a retrospective study. Associations between specific macrolides and OHCA were examined by conditional logistic regression analyses in case-crossover and case–time–control models, using penicillin-V treatment as the comparative reference. From nationwide registries, we identified all OHCAs in Denmark from 2001 to 2010 and use of antibiotics. ETHICS: The present study was approved by the Danish Data Protection Agency (Danish Data Protection Agency (ref.no. 2007-58-0015, local ref.no. GEH-2014-017, (I-Suite.nr. 02 735)). PARTICIPANTS: We identified 29 111 patients with an OHCA. Of these, 514 were in macrolide treatment ≤7 days before OHCA and 1237 in penicillin-V treatment. RESULTS: In the case-crossover analyses, overall macrolide use was not associated with OHCA with penicillin V as negative comparative reference (OR=0.90; 95% CI 0.73 to 1.10). Compared with penicillin-V treatment, specific macrolides were not associated with increased risk of OHCA: roxithromycin (OR=0.97; 95% CI 0.74 to 1.26), erythromycin (OR=0.68; 95% CI 0.44 to 1.06), clarithromycin (OR=0.95; 95% CI 0.61 to 1.48) and azithromycin (OR=0.85; 95% CI 0.57 to 1.27). Similar results were obtained using case–time–control models: overall macrolide use (OR=0.81; 95% CI 0.62 to 1.06) and specific macrolides (roxithromycin (OR=0.70; 95% CI 0.49 to 1.00), erythromycin (OR=0.67; 95% CI 0.38 to 1.18), clarithromycin (OR=0.75; 95% CI 0.41 to 1.39) or azithromycin (OR=1.17; 95% CI 0.70 to 1.95)). CONCLUSION: The risk of OHCA during treatment with macrolides was similar to that of penicillin V, suggesting no additional risk of OHCA associated with macrolides.