PROTON-PUMP INHIBITORS ARE ASSOCIATED WITH INCREASED CARDIOVASCULAR RISK INDEPENDENT OF CLOPIDOGREL USE

Title: Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use: A Nationwide Cohort Study
Date Posted: October 8, 2010
Authors: Charlot M, Ahlehoff O, Norgaard ML et al.
Citation: Ann Intern Med 2010;153:378-386.


Clinical Trial:
Clopidogrel and the Optimization of Gastrointestinal Events Trial

Study Question:
What is the risk for adverse cardiovascular outcomes related to concomitant use of proton pump inhibitors (PPIs) and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction (MI)?

Methods:
This was a nationwide cohort study based on linked administrative registry data. The primary outcome was a composite of rehospitalization for MI or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after MI. Follow-up was 1 year.

Results:
Of 56,406 included patients, 9,137 (16.2%) were rehospitalized for MI or stroke or experienced cardiovascular death. Of the 24,702 patients (43.8%) who received clopidogrel, 6,753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for MI or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% confidence interval, 1.17-1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21-1.37). No statistically significant interaction occurred between a PPI and clopidogrel (p = 0.72).

Conclusions:
The authors concluded that PPIs seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for MI.

Perspective:
This study found no evidence that concomitant PPI therapy increases risk for adverse cardiovascular events in patients who receive clopidogrel and is consistent with the results of the COGENT trial. PPIs appear to be associated with an increased risk for adverse cardiovascular outcomes regardless of clopidogrel use, and this increased cardiovascular risk is likely explained by unmeasured confounders. These results seem to refute concerns about increased risk for ischemic events during concomitant PPI and clopidogrel therapy, and provide further reassurance about safety of PPIs in patients on dual antiplatelet therapy when such therapy is indicated.