Background Clopidogrel is an approved antiplatelet agent used in the treatment of atherothrombotic disease. Proton pump inhibitors (PPIs) are often prescribed in combination with clopidogrel. The use of omeprazole is associated with decreased antiplatelet activity and adverse clinical outcomes of clopidogrel because of cytochrome P450 (CYP) 2C19 interaction.

Purpose The authors investigated the effect of switching from omeprazole to pantoprazole on the clopidogrel response expressed as the platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein phosphorylation.

Materials and methods Clopidogrel users (N=25) switched from omeprazole to pantoprazole and were given pantoprazole 40 mg daily for this prospective, prepost cohort study. Data collected were age, clopidogrel indication, PRI results, comorbidities, comedication and CYP2C19 genotype (*2, *3 mutations). Primary end point was PRI of clopidogrel which was measured on the day before switching and after at least three weeks of pantoprazole use.

Results Clopidogrel users taking pantoprazole had a significantly lower mean PRI than during the omeprazole period (difference PRI 4.6%; 95% CI (CI95) 1.0-8.2%; P=0.015; figure 1). The mean PRI was also significantly higher in CYP2C19*2 allele carriers compared to the wildtype CYP2C19 group during omeprazole (difference PRI 16.7%; CI95 3.7-29.7%; P=0.014) and pantoprazole use (difference PRI 17.4%; CI95 2.4-32.5%; P=0.025).

Conclusions In this study switching from omeprazole to pantoprazole resulted in better clopidogrel response. Patients with variant CYP2C19 alleles had a significantly higher clopidogrel PRI when using omeprazole or pantoprazole compared to wildtype patients. If a PPI is indicated, clopidogrel users should use pantoprazole instead of omeprazole.