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Proton Pump Inhibitors and Clopidogrel: Bad Company?

In a large observational cohort of ACS patients, this drug combination was associated with poorer outcomes than was clopidogrel alone.

Proton pump inhibitors (PPIs) are often prescribed to minimize gastrointestinal bleeding in patients taking clopidogrel after acute coronary syndromes. However, findings from small studies suggest that PPIs may reduce clopidogrel’s efficacy. To determine whether such an interaction could have important clinical effects, investigators assessed outcomes in 8025 patients with ACS who were discharged from Veterans Affairs hospitals nationwide and who received clopidogrel with or without a PPI. The primary outcome was the composite of all-cause mortality and rehospitalization for ACS.

A majority (63.9%) of the patients were prescribed a PPI in conjunction with clopidogrel. In multivariable analysis, the use of a PPI with clopidogrel was associated with a significantly increased risk for the primary outcome compared with clopidogrel alone (odds ratio, 1.25; 95% confidence interval, 1.11–1.41). Secondary analyses suggested that these findings were driven by increases in hospitalization for recurrent ACS and in revascularization procedures but not in all-cause mortality. Use of a PPI without clopidogrel was not associated with adverse outcomes.

Comment: In this large, retrospective study, the use of PPIs appeared to attenuate the benefits of clopidogrel, resulting in increased rates of recurrent ACS and revascularization. Although these results bear the limitations of all observational studies, they support the hypothesis that PPIs inhibit the antiplatelet effects of clopidogrel. Pending further research, clinicians should consider this potential interaction when they weigh the pros and cons of prescribing a PPI with clopidogrel for ACS patients.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology March 3, 2009

Citation(s):

Ho PM et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009 Mar 4; 301:937.

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• Is this a class effect?
  Ronald L Hirsch, 8 May 2009 9:00 AM EST
  The Canadian Medical Assn. Journal had an study in early 2009 that this was not a class effect- Pantoprazole does... [more]