Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study.
OBJECTIVE
This study sought to compare the effect of 2 proton pump inhibitors (PPIs) on platelet response to clopidogrel after coronary stenting for non-ST-segment elevation acute coronary syndrome (NSTE ACS).


BACKGROUND
Use of omeprazole has been reported to significantly decrease the clopidogrel antiplatelet effect because of cytochrome P450 interaction. Because all PPIs are metabolized by CYP2C19, but to a varying degree, we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be caused by a class effect.


METHODS
A total of 104 patients undergoing coronary stenting for NSTE ACS were prospectively included and randomized to omeprazole or pantoprazole 20 mg. They received at discharge 75-mg aspirin and 150-mg clopidogrel. Platelet reactivity index (PRI) vasoactive stimulated phosphoprotein (VASP) was used to assess clopidogrel response and adenosine diphosphate (ADP)-induced aggregation for platelet reactivity (ADP-Ag).


RESULTS
After 1 month, patients receiving pantoprazole had a significantly better platelet response to clopidogrel as assessed with the PRI VASP: 36 +/- 20% versus 48 +/- 17% (p = 0.007). We identified more clopidogrel nonresponders in the omeprazole group than in the pantoprazole group: 44% versus 23% (p = 0.04), odds ratio: 2.6 (95% confidence interval: 1.2 to 6.2). Conversely, we did not observe any significant difference in platelet reactivity with ADP-Ag between the omeprazole and pantoprazole groups: 52 +/- 15% and 50 +/- 18%, respectively (p = 0.29).


CONCLUSIONS
The present findings suggest the preferential use of pantoprazole compared with omeprazole in patients receiving clopidogrel to avoid any potential negative interaction with CYP2C19.
Cuisset
Thomas
T
Département de Cardiologie, CHU Timone, Marseille, France.
Frere
Corinne
C
Quilici
Jacques
J
Poyet
Raphael
R
Gaborit
Bénédicte
B
Bali
Laurent
L
Brissy
Olivier
O
Morange
Pierre-Emmanuel
PE
Alessi
Marie-Christine
MC
Bonnet
Jean-Louis
JL
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D054058:Acute Coronary Syndrome / Q000628:therapy*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000077144:Clopidogrel; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology*; D000077402:Pantoprazole; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D000077402:Pantoprazole; D009853:Omeprazole; D013988:Ticlopidine