Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome

Pharmacoepidemiol Drug Saf. 2011 Oct;20(10):1043-9. doi: 10.1002/pds.2202. Epub 2011 Aug 8.


Background: There is conflicting evidence regarding the potential interaction between clopidogrel and proton pump inhibitors (PPIs), with observational studies suggesting an increased risk of adverse cardiovascular (CV) outcomes and clinical trials suggesting there is no such risk.

Methods: We conducted a retrospective cohort study to assess CV outcomes of 9753 patients taking dual antiplatelet therapy of aspirin plus clopidogrel with or without a PPI after hospitalization for acute coronary syndrome (ACS). Cox proportional hazards models were used to assess our primary endpoint of re-hospitalization for ACS in overall sample and a propensity score matching subsample.

Results: Among patients taking clopidogrel plus aspirin, concomitant use of PPI was not associated with the risk of re-hospitalization for ACS (adjusted hazard ratio [HR] 1.12 [95%CI 0.72-1.73]). The findings were consistent in the propensity score matching cohort (adjusted HR 0.82 [95%CI 0.43-1.54]). Compared with PPI nonusers, there is no significant association between each specific PPI users and the risk of re-hospitalization for ACS (adjusted HR; omeprazole 0.96 [95%CI 0.35-2.66], pantoprazole 1.05 [95%CI 0.38-2.92], rabeprazole 0.60 [95%CI 0.17-2.17], esomeprazole 0.31 [95%CI 0.10-0.99], and lansoprazole 0.82 [95%CI 0.32-2.07]).

Conclusion: In conclusion, this population-based cohort study found that concomitant use of clopidogrel and PPI in patients who received dual antiplatelet therapy after ACS was not associated with risk of ACS re-hospitalization. Together, our study and findings of recently published clinical trials suggest that there was no apparent CV interaction between clopidogrel and PPI in patients who received dual antiplatelet therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / epidemiology*
  • Aged
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Aspirin / therapeutic use
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / epidemiology
  • Clopidogrel
  • Cohort Studies
  • Cytochrome P-450 CYP2C19
  • Databases, Factual
  • Drug Interactions
  • Esomeprazole
  • Female
  • Herb-Drug Interactions
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Omeprazole / adverse effects
  • Omeprazole / therapeutic use
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Recurrence
  • Retrospective Studies
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Omeprazole
  • Esomeprazole
  • Ticlopidine
  • Aspirin