Risk of recurrent myocardial infarction with the concomitant use of clopidogrel and proton pump inhibitors

Aliment Pharmacol Ther. 2011 Jan;33(1):77-88. doi: 10.1111/j.1365-2036.2010.04485.x. Epub 2010 Oct 19.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Clopidogrel
  • Combined Modality Therapy / adverse effects*
  • Confounding Factors, Epidemiologic
  • Drug Interactions*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / complications*
  • Myocardial Infarction / drug therapy
  • Platelet Aggregation Inhibitors / adverse effects*
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Recurrence
  • Regression Analysis
  • Risk Factors
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Young Adult


  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Ticlopidine