NEW YORK (Reuters Health) – Interactions between clopidogrel and proton pump inhibitors (PPI) appear to have only a small effect, if any, in older patients, report researchers from Boston’s Brigham and Women’s Hospital.

PPI activity against the cytochrome P450 enzyme CYP2C19, which has a key role in clopidogrel metabolism, is thought to underlie “clopidogrel resistance” – which is why lead author Dr. Jeremy A. Rassen and his colleagues undertook their study.

“Our analysis did not demonstrate a large or statistically significant increase in the relative risk of myocardial infarction hospitalization or death for patients treated concurrently with clopidogrel and a PPI, but it was consistent with the possibility of a modest clinical effect,” Dr. Rassen told Reuters Health. “One prudent strategy would be to co-prescribe PPIs primarily in those clopidogrel-treated patients at higher risk of adverse gastrointestinal events.”

Dr. Rassen and his colleagues analyzed health insurance data on 18,565 patients aged 65 years and older to determine whether there was a higher rate of myocardial infarction, revascularization, and death in patients taking clopidogrel with a PPI compared to those taking clopidogrel alone.

In the December 8th issue of Circulation, they report, “On a pooled basis, 2.6% of those who…initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization.”

Adjusted for propensity score, rate ratios were 1.22 for the primary endpoint of myocardial infarction or death, 1.20 for death, and 0.97 for revascularization.

“Although the point estimates…indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, the possible increase in risk was modest, the confidence intervals were wide, and we did not observe consistent evidence of a substantial or statistically significant clopidogrel-PPI interaction,” the investigators conclude in their paper.

With regard to choice of PPI, research has shown that pantoprazole is less likely than omeprazole to inhibit CYP2C19. Dr. Rassen added, “Our study did not show a meaningful difference between pantoprazole-clopidogrel and omeprazole-clopidogrel with regard to the risk of MI hospitalization or death, so our data indicate that while the pantoprazole-clopidogrel combination may or may not lower the potential risk associated with clopidogrel and PPIs, it also should not raise it.”

In an editorial, Dr. David N. Juurlink from the University of Toronto, Ontario, Canada, writes, “For clinicians uncertain how to address this drug interaction in practice, I propose 3 simple steps: 1. Evaluate the necessity of PPI therapy… 2. Consider using pantoprazole when a PPI is indicated… 3. Stagger the dosing of medication.”

“As we await further research on the phenomenon of drug-induced clopidogrel resistance, a cautious approach that exploits the basic pharmacology of these drugs is a sensible and easily achievable way to safely prescribe PPIs in patients taking clopidogrel,” the editorial concludes.

Reference:
Circulation 2009;120: 2310-2312,2322-2329.