To prevent gastrointestinal bleeding as a drug-induced side effect, proton pump inhibitors (PPI) are often associated with clopidogrel use. This strategy is recommended by consensus guidelines and endorsed by a recent meta-analysis, especially for patients taking dual antiplatelet therapy. Several retrospective observational studies showed an increased risk of new cardiovascular events in patients on clopidogrel-PPI association thus leading the United States Food and Drug Administration and the European Medicines Agency to recommend to avoid the clopidogrel-PPI combination, especially with omeprazole.

A pilot randomized trial published in the International Journal of Cardiology (Jun 2012) evaluated the influence of pantoprazole, indicated as relatively less influent than other Proton Pump Inhibitors(PPIs), on the antiplatelet effect of clopidogrel (considering a stratification of the population for the presence of cytochrome 2C19*2 polymorphism since CYP2C19*2 polymorphism is significantly associated with residual platelet reactivity).
The study found that pantoprazole increases the ADP-MA (adenosin diphosphate -ADP)(MA- maximal aggregation) in patients treated with dual antiplatelet therapy.

Researchers evaluated 105 patients with ST elevation myocardial infarction (STEMI), treated with percutaneous coronary angioplasty (PCI) and who received dual antiplatelet therapy, were randomized between pantoprazole (n=54) or ranitidine (n=51).

Demographic, clinical and procedural data and the prevalence of CYP2C19*2 polymorphism were similar between the two groups. The researchers observed a significant increase in MA values with ADP in PPI group at 5days (p=0.01) and 30 days (p=0.03). At the multiple regression analysis PPI use remained significantly associated with ADP-MA both at 5 days (p=0.05) and 30 days (p=0.03).