Effect of clarithromycin versus placebo on risk of atrial fibrillation

INTRODUCTION: The CLARICOR randomised trial of clarithromycin versus placebo in patients with stable ischaemic heart disease found increased all-cause and cardiovascular mortality after a brief clarithromycin regimen, suggesting a possible arrhythmic effect. As atrial fibrillation (AF) is the most common arrhythmia and a major contributor to cardiovascular morbidity and mortality, we compared the AF incidence in the randomisation groups in a post-hoc analysis.

METHODS: In 1999-2000, a total of 4,372 patients with stable ischaemic heart disease were randomised to a two-weeks course of clarithromycin or placebo. Incident AF episodes were followed for ten years through national registers. Using Cox proportional hazard models and some subsidiary analyses, we assessed the effect of clarithromycin on occurrence of AF.

RESULTS: Among participants, 285 (13.5%) patients in the clarithromycin group and 271 (13.3%) patients in the placebo group were recorded to have (at least) one AF period during follow-up. The Cox analysis showed no significant difference in AF incidence between groups (HR = 1.09; 95% CI: 0.92-1.29; p = 0.32), consistent with findings in the subsidiary analyses.

CONCLUSIONS: In this post-hoc analysis, a brief course of clarithromycin did not increase the incidence of new AF in participants with chronic stable ischaemic heart disease.

FUNDING: The present study was financed by the Copenhagen Trial Unit, Centre for Clinical Intervention Research, the Capital Region, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

CLINICALTRIALS: gov, NCT00121550.