Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel

Aliment Pharmacol Ther. 2010 Apr;31(8):810-23. doi: 10.1111/j.1365-2036.2010.04247.x. Epub 2010 Jan 22.


Background: Recent studies have suggested an adverse interaction between proton pump inhibitors (PPI) and clopidogrel.

Aim: To perform a meta-analysis of cardiovascular outcomes and mortality in patients taking clopidogrel, with and without concomitant PPI.

Methods: We searched MEDLINE, EMBASE, Cochrane Controlled Trials Register in October 2009, and checked conference abstracts for randomized and nonrandomized studies that reported the risk of cardiovascular events and mortality with PPI exposure in patients taking clopidogrel. We performed random effects meta-analysis, stratified by study design and assessed heterogeneity using the I2 statistic.

Results: Our review included 23 studies covering 93,278 patients. There was substantial heterogeneity in the meta-analyses of major cardiovascular events (19 studies, I2 = 79%) or myocardial infarction (12 studies, I2 = 77%). Analysis of propensity-matched or randomized trial participants showed no associated cardiovascular risk with PPIs, whereas other observational studies generally showed a significant association. Meta-analysis of 13 studies showed no significant association between PPI use and overall mortality (RR 1.09, 95% CI: 0.94-1.26, P = 0.23, I2 = 60%).

Conclusion: As there are conflicting and inconsistent data regarding the adverse clopidogrel-PPI interaction, clinicians should focus on potential harm from ulcers/haemorrhage before deciding to omit PPIs in patients taking clopidogrel.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Aged
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / mortality
  • Clopidogrel
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects*
  • Proton Pump Inhibitors / adverse effects*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome


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