One-year clinical outcome in patients with acute coronary syndrome treated with concomitant use of clopidogrel and proton pump inhibitors: results from a regional cohort study

J Cardiovasc Med (Hagerstown). 2012 Dec;13(12):783-9. doi: 10.2459/JCM.0b013e3283416b6b.


Objectives: We sought to compare the 1-year risk of re-hospitalization for acute coronary syndrome (ACS) between patients taking clopidogrel with proton pump inhibitors (PPIs) vs. clopidogrel without PPIs.

Materials and methods: We conducted a retrospective cohort study among 3896 patients with ACS, at low risk for gastrointestinal bleeding, discharged from all hospitals of the Emilia-Romagna region of Italy during the period January-August 2008. Patients' consumption of clopidogrel and PPIs at hospital discharge and follow-up was based on pharmacy refill data. Of these 3896 patients, 90% (n = 3519) were prescribed PPIs at hospital discharge and/or at some time during follow-up.

Results: At 1-year follow-up, hospitalization for ACS occurred in 15% of patients taking clopidogrel with PPIs vs. 3.4% of those taking clopidogrel without PPIs (P < 0.001). No difference in terms of all-cause mortality could be detected between the two groups. At multivariate regression analysis with PPI use as a time-varying covariate, periods of use of clopidogrel with PPIs were associated, at 1-year follow-up, with a significantly higher risk of hospitalization for ACS (hazard ratio 1.29, P = 0.025). Notably, this event occurred mostly in patients who underwent revascularization during the index hospitalization (n = 3045, hazard ratio 1.52, P = 0.004). No significant effect of PPI prescription could be observed in terms of 1-year all-cause mortality and revascularization.

Conclusion: This study suggests the hypothesis that a concomitant use of clopidogrel and PPIs in patients with ACS, at low risk for gastrointestinal bleeding, having mostly undergone coronary revascularization, is associated with an approximately 30% higher risk of nonfatal hospitalization for ACS.

Publication types

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

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / mortality
  • Aged
  • Aged, 80 and over
  • Chi-Square Distribution
  • Clopidogrel
  • Drug Interactions
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / prevention & control
  • Humans
  • Italy
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Patient Readmission
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Proportional Hazards Models
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome


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