Clopidogrel and proton pump inhibitors - where do we stand in 2012?

Table 1 Overview of important pharmacodynamic studies on the clopidogrel-proton pump inhibitor interaction

Study	PPIs used	Population	Primary outcome	Author’s conclusions
Gilard et al[7] OCLA study (double-blind, placebo-controled, randomized)	Omeprazole	124 patients undergoing elective coronary stent implantation	VASP-PRI on 7 d	Omeprazole significantly decreases clopidogrel inhibitory effect
Cuisset et al[11] PACA study (prospective, randomized)	Omeprazole vs Pantoprazole	104 NSTE-ACS patients undergoing coronary stenting	VASP-PRI/ADP-Ag after 1 mo	Significantly better platelet response under pantoprazole (VASP-PRI), no difference for ADP-Ag
O’Donoghue et al[26] PRINCIPLE-TIMI 44 (post hoc analysis of a RCT)	Not specified	201 patients undergoing planned PCI	ADP Ag	Mean inhibition of platelet aggregation significantly lower for patients on PPI
Siller-Matula et al[8] (prospective observational)	Pantoprazole esomeprazole	300 patients with CAD undergoing PCI	VASP-PRI/ADP-Ag in the catheter laboratory	No association of PPIs with impaired response to clopidogrel
Neubauer et al[13] (prospective observational)	Pantoprazole omeprazole esomeprazole	336 patients undergoing coronary stent implantation	ADP Ag	Pantoprazole does not diminish the antiplatelet effectiveness of clopidogrel
Angiolillo et al[12] (placebo controlled, randomized, cross-over)	Omeprazole pantoprazole	282 healthy subjects	Clopi H4 ADP Ag VASP-PRI after 5 d	Presence of a metabolic drug-drug interaction between clopidogrel and omeprazole but not for pantoprazole

VASP-PRI: Vasodilator-stimulated phosphoprotein platelet reactivity index; NSTE-ACS: Non-ST-elevation acute coronary syndrome; ADP Ag: Adenosine DiPhospate induced platelet aggregation; CAD: Coronary artery disease; PCI: Percutaneous coronary intervention; PPI: Proton pump inhibitor; OCLA: Omeprazole Clopidogrel Aspirine; PACA: PPI and clopidogrel association; PRINCIPLE-TIMI: Prasugrel in comparison to clopidogrel for inhibition of platelet activation and aggregation-TIMI.