Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study

OBJECTIVE: To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics. DESIGN: Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication. SETTING: Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES). PARTICIPANTS: Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998–2012 and eligible for data linkage to HES. MAIN OUTCOME MEASURES: The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and all-cause mortality. RESULTS: Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22. CONCLUSIONS: CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics.