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Aliment Pharmacol Ther 2011; 33: 77–88

Summary

Background  The association between myocardial infarction (MI) and co-administration of proton pump inhibitors (PPIs) and clopidogrel remains controversial.

Aim  To quantify the association between concomitant use of PPIs and clopidogrel and occurrence of recurrent MI.

Methods  We conducted a case–control study within a cohort of acute MI patients in PHARMO Record Linkage System (1999–2008). The cases were patients readmitted for MI. PPI exposure was categorized as current (3–1 days before MI), past (30–3 days before MI), or no use (>30 days before MI). We used conditional logistic regression analyses.

Results  Among 23 655 patients hospitalized following MI, we identified 1247 patients readmitted for MI. Among clopidogrel users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.62, 95% CI: 1.15–2.27) when compared with no PPI use, but not when compared with past PPI use (OR: 0.95, 95% CI: 0.38–2.41). Among clopidogrel non-users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.38, 95% CI: 1.18–1.61) when compared with no PPI use.

Conclusions  The apparent association between recurrent MI and use of PPIs with clopidogrel depends on the design, and is affected by confounding by indication. The association is not present when (un)measured confounding is addressed by design.