Long-term risk of acute myocardial infarction, stroke and death with outpatient use of clarithromycin: a retrospective cohort study

ABSTRACT

This retrospective cohort study of subjects enrolled in the United Kingdom Clinical Practice Research Datalink from 2000-2013 evaluated long-term risks of death, stroke, and acute myocardial infarction (AMI) in adults prescribed clarithromycin. Subjects were outpatients aged 40-85 years prescribed clarithromycin, doxycycline, or erythromycin (287,748, 267,729, and 442,999 patients, respectively), or H. pylori eradication therapy with a proton pump inhibitor, amoxicillin, and either clarithromycin (27,639 patients) or metronidazole (14,863 patients). We analyzed time to death, stroke, or AMI with Cox proportional hazards regression. The long-term hazard ratio (HR) for death following one clarithromycin versus one doxycycline prescription was 1.29 (95% confidence interval (CI) 1.21, 1.25), increasing to 1.62 (95% CI 1.43, 1.84) for 5+ prescriptions of clarithromycin versus 5+ prescriptions for doxycycline. Erythromycin showed smaller risks versus doxycycline. Stroke and AMI were also increased after clarithromycin, but with smaller HRs than mortality. For H. pylori eradication, the HR for mortality following clarithromycin versus metronidazole regimens was 1.09 (95% CI 1.00, 1.18) overall, and was higher (1.65, 95% CI 0.88, 3.08) following 2+ prescriptions in subjects not on statins at baseline. Outpatient clarithromycin use was associated with long-term mortality increases, with evidence for a similar, smaller increase with erythromycin.

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