Interaction between clopidogrel and proton pump inhibitors

David Juurlink and colleagues showed that among patients receiving clopidogrel following an acute myocardial infarction, current users of proton pump inhibitors had an increased risk of re-infarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03–1.57).¹ A further analysis by type of proton pump inhibitor showed that this effect was not seen with pantoprazole (adjusted OR 1.02, 95% CI 0.70–1.47) but only with other proton pump inhibitors (OR 1.40, 95% CI 1.10–1.77). The authors concluded that proton pump inhibitors other than pantoprazole negate the therapeutic effect of clopidogrel in such patients.

However, the difference between the effect of pantoprazole and that of the other proton pump inhibitors is not statistically significant. The point estimate of the effect of the other proton pump inhibitors lies within the 95% CI associated with the effect of pantoprazole. A formal test for heterogeneity of these ORs² also shows no statistically significant difference between the effect of pantoprazole and that of the other proton pump inhibitors (χ²= 2.99, 1 degree of freedom, p = 0.08).

Although this study indicates that concurrent use of proton pump inhibitors and clopidogrel is associated with increased risk of recurrent myocardial infarction, it does not contain definitive evidence to make a distinction between the clopidogrel-inhibiting effects of pantoprazole and other proton pump inhibitors. More research is needed to elucidate the mechanism of action of the interaction between clopidogrel and proton pump inhibitors and to determine whether some proton pump inhibitors are safer than others.