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Adverse Outcome..

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It is estimated that in 2005 there were 772,000 to 1.4 million hospital discharges for acute coronary syndromes (ACS).1 Clopidogrel is commonly used in these patients to reduce the risk of recurrent cardiovascular events. Patients who are at high risk of gastrointestinal bleeding, especially those receiving dual antiplatelet therapy, are often prescribed a proton pump inhibitor (PPI) in addition to clopidogrel. Recently, it has been suggested that the effectiveness of clopidogrel may be attenuated by PPIs.2,3 While the exact mechanism of the interaction is still unknown, reports suggest that some PPIs may inhibit the cytochrome p450 enzyme that is responsible for converting clopidogrel into its active metabolite. However, not all studies have found a decrease in clopidogrel efficacy when given concomitantly with PPIs.4

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Ho and colleagues recently published the results of a retrospective cohort study that assessed the outcomes of patients prescribed clopidogrel with or without a PPI.5 Data were reviewed for patients discharged from any Veterans Health Administration hospital between October 1, 2003, and January 31, 2006, with a diagnosis of acute myocardial infarction (MI) or unstable angina and who filled a prescription for clopidogrel through the VA outpatient pharmacy. The combined endpoint of all-cause mortality or rehospitalization for ACS was the primary outcome under investigation. Secondary outcomes included the individual components of the primary outcome, as well as revascularization procedures.

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In the study, 8205 patients were identified who were prescribed clopidogrel after hospital discharge for ACS. Almost two-thirds of the patients (n=5244) were prescribed a PPI at discharge, during follow-up, or both. Patients prescribed clopidogrel with a PPI were slightly older than patients prescribed clopidogrel without a PPI (67.7 yrs vs 65.7 yrs, p<0.001) and were more likely to have comorbid conditions. Over 98% of patients were male. At discharge, there was no difference in the use of beta-blockers, ACE inhibitors, or statins between patients prescribed clopidogrel with a PPI and patients prescribed clopidogrel without a PPI. However, aspirin use at discharge was slightly higher among patients on clopidogrel without a PPI (91.2% vs 89.4%, p=0.01).

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The primary outcome of all-cause mortality or rehospitalization for ACS occurred in 29.8% of patients prescribed clopidogrel with a PPI and in 20.8% of patients prescribed clopidogrel without a PPI. After adjusting for differences in baseline characteristics, the concomitant use of clopidogrel with a PPI was associated with a 25% increase in the odds of death or rehospitalization for ACS (adjusted odds ratio 1.25, 95% confidence interval 1.11-1.41). The increased risk appears to be primarily due to rehospitalization for ACS (adjusted odds ratio 1.86, 95% confidence interval 1.57-2.20). No association was found for all-cause mortality between patients prescribed clopidogrel with a PPI and those prescribed clopidogrel without a PPI (adjusted odds ratio 0.91, 95% confidence interval 0.80-1.05).

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A majority of the patients prescribed a PPI were prescribed omeprazole (59.7%) or rabeprazole (2.9%). Investigators noted a consistent association between use of clopidogrel and omeprazole with adverse outcomes. A similar association was found between use of clopidogrel and rabeprazole; however, the sample size was much smaller. Conclusions regarding other PPIs could not be drawn due to the small numbers of patients prescribed those agents. The investigators also found that longer duration of treatment with a PPI was associated with an increased risk of death or rehospitalization. This finding needs further investigation.

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To summarize, this study found an increased risk of death or rehospitalization ...

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