Figure 1. Proposed mechanism for DAPT/PPI drug interaction.

Clopidogrel is metabolized by cytochrome CYP450 2C19. Omeprazole has inhibitory effects and is metabolized by CYP450 2C19, therefore, potentially limiting the active form of clopidogrel and its antiplatelet effects. Omeprazole inhibits the H+/K+-ATPase on the luminal side of parietal cells, which decreases the acid production in the stomach. This could limit the absorption of aspirin. On its own, aspirin increases the risk of UGIB by decreasing mucus secretion, decreased bicarbonate secretion, and decreasing mucosal blood flow. The addition of PPI to aspirin typically works to decrease the risk of ulcer formation via decreased acid production. Omeprazole has the potential to affect the absorption and metabolism of aspirin and clopidogrel, respectively. Created with BioRender.com.

DAPT, dual-antiplatelet therapy; PPI, proton pump inhibitor; UGIB, upper gastrointestinal bleed; COX1, cyclooxygenase-1; H+/K+-ATPase, hydrogen potassium adenosine triphosphatase.