Although the overall trial33 failed to demonstrate a significant difference in the primary endpoint between the clopidogrel and aspirin groups (4.2% versus 4.4%), the PCI subset (n 17 263) did show significant differences in the clopidogrel arm.32 The primary outcome was reduced in the PCI subgroup randomized to higher-dose clopidogrel (3.9% versus 4.5%; P 0.035), and this was largely driven by a reduction in myocardial (re)infarction (2.0% versus 2.6%; P 0.017). Definite stent thrombosis was reduced in the higher-dose clopidogrel group (0.7% versus 1.3%; P 0.0001), with consistent results across DES versus non-DES subtypes. Higher-dose clopidogrel therapy in- creased major bleeding in the entire group (2.5% versus P 0.008). The benefit of higher-dose clopidogrel loading was offset by an increase in major bleeding.32 The findings from the prespecified PCI subgroup analysis32 should be interpreted with caution and considered hypothesis generat- ing, because the primary endpoint of the CURRENT OASIS 7 trial was not met and given that the P value for interaction (P 0.026) between treatment effect and PCI was of border- line statistical significance. As noted in the dosing table (Appendix 3), the current recommended loading dose for clopidogrel is uncertain. In addition, several hours are required to metabolize clopidogrel to its active metabolite, leaving a window of time where there is a reduced level of effectiveness even in patients who respond to clopidogrel. 3.2.3.1.5. Proton Pump Inhibitors and Dual Antiplatelet Therapy for ACS. Proton pump inhibitor (PPI) medications have been found to interfere with the metabolism of clopi- dogrel. 