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Publication Briefs

Concomitant Use of Clopidogrel and Proton-Pump Inhibitors after ACS is Associated with Higher Risk of Adverse Outcomes


  • Proton-pump inhibitors (PPI) were frequently prescribed with clopidogrel (63.9%) for Veterans following hospitalization for acute coronary syndrome (ACS); the concomitant use of clopidogrel and PPI was associated with a higher risk of adverse outcomes compared to the use of clopidogrel alone.
  • The combined primary outcome of mortality or re-hospitalization occurred in 20.8% of Veterans prescribed clopidogrel only, and in 29.8% of Veterans prescribed clopidogrel and PPI.
  • Among secondary outcomes, Veterans taking clopidogrel and PPI also had a higher risk of recurrent hospitalization for ACS and revascularization procedures.
  • Longer duration of clopidogrel plus PPI treatment was associated with adverse outcomes, suggesting that time on combination treatment is important.
  • Pending further studies to confirm results and prospectively assess cardiovascular outcomes for Veterans taking clopidogrel and PPI versus clopidogrel alone, these results may suggest that PPIs should be used for patients with a clear indication for the medication, rather than prophylactically.

Treatment with clopidogrel in addition to aspirin reduces recurrent cardiovascular events following ACS hospitalization for patients treated either medically or with percutaneous coronary intervention. Proton-pump inhibitor (PPI) medications are often prescribed prophylactically with initiation of clopidogrel, with the goal of reducing the risk of gastrointestinal bleeding while on dual anti-platelet therapy. However, there is controversy regarding the outcomes of patients taking clopidogrel and PPIs. The FDA recently released an early communication about a safety review of the potential interaction between these two medications, but there was insufficient evidence to make any recommendations. This retrospective cohort study assessed the outcomes of Veterans taking clopidogrel with or without PPI following ACS hospitalization. Investigators examined all-cause mortality or re-hospitalization for 8,205 Veterans discharged on clopidogrel from 127 VA hospitals from 2003-2006.


  • Data on recurrent ACS or revascularization outside VA, and cause-specific mortality data were not available.
  • Due to the observational study design, causality cannot be concluded, and individual patient benefits of clopidogrel plus PPI therapy cannot be addressed.

This study was funded through VA/HSR&D's Ischemic Heart Disease Quality Enhancement Research Initiative (IHD-QUERI). Dr. Ho also is supported by an HSR&D Career Development Award. Drs. Fihn, Jesse, Peterson, and Rumsfeld are part of IHD-QUERI.

March 4, 2009 in JAMA

PubMed Logo Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, Rumsfeld JS. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009 Mar 4;301(9):937-44.

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HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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