Pantoprazole significantly interferes with antiplatelet effect of clopidogrel: results of a pilot randomized trial.
BACKGROUND
The CYP2C19*2 polymorphism is significantly associated with residual platelet reactivity (RPR) and maybe a major confounding factor in studies evaluating pharmacological interactions with clopidogrel.


OBJECTIVE
We sought to evaluate the influence of a proton pump inhibitor (PPI), pantoprazole, indicated as relatively less influent than other PPIs, on the antiplatelet effect of clopidogrel, considering a stratification of the population for the presence of cytochrome 2C19*2 polymorphism.


METHODS
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). RPR was evaluated by Platelet Function Analyzer-100 (PFA-100) with collagen-epinephrine (CEPI) and collagene-ADP (CADP) cartridges and by light transmitted aggregometry with 10 μM adenosin diphosphate (ADP) and 1mM arachidonic acid (AA), on 5 (T0) and 30 (T1) days after PCI.


RESULTS
Demographic, clinical and procedural data and the prevalence of CYP2C19*2 polymorphism were similar between the two groups. Not statistically differences were observed for CEPI-CT and for the maximal aggregation (MA) values with AA stimulus at both times. We observed a significant increase in MA values with ADP in PPI group at T0 (p=0.01) and T1 (p=0.03). At the multiple regression analysis PPI use remained significantly associated with ADP-MA both at T0 (p=0.05) and T1 (p=0.03).


CONCLUSIONS
This is the first documentation in a randomized trial, after correction for the bias of CYP2C19*2 polymorphism, that pantoprazole increases the ADP-MA in patients treated with dual antiplatelet therapy.
Fondazione Toscana G Monasterio, Ospedale G. Pasquinucci, Massa, Italy. parri@ifc.cnr.it
Maria Serena
MS
Parri
Jacopo
J
Gianetti
Anar
A
Dushpanova
Francesca
F
Della Pina
Claudia
C
Saracini
Rossella
R
Marcucci
Betti
B
Giusti
Sergio
S
Berti
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000097:blood*; D000368:Aged; D000077144:Clopidogrel; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D000077402:Pantoprazole; D010865:Pilot Projects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood*; D010979:Platelet Function Tests / Q000379:methods; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000097:blood*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D000077402:Pantoprazole; D013988:Ticlopidine