Circulation: Cardiovascular Interventions Topic Review Circulation: Cardiovascular Interventions Editors’ Picks: Most Important Papers in Antiplatelet Therapy

A growing body of evidence has shown a broad variability in interindividual pharmacodynamic response profiles to the platelet inhibitor clopidogrel, and patients with reduced platelet inhibition have an increased risk of recurrent atherothrombotic events. Numerous factors may contribute to poor clopidogrel response. Among these, that secondary to a drug interaction with the proton pump inhibitor omeprazole has emerged. The prognostic implications associated with clopidogrel and omeprazole use are not fully elucidated. However, given the high frequency with which both these drugs are prescribed, even a small and limited impairment in clinical outcomes can potentially affect a large number of patients. The Food and Drug Administration and the European Medicines Agency have recently recommended avoidance of this drug combination. Nevertheless, because both clopidogrel and omeprazole are rapidly metabolized, many experts have hypothesized and proposed to stagger clopidogrel and omeprazole intake to minimize or even overcome their interaction. However, this strategy has not been validated yet and represents the rationale for the present study design. The findings of the present investigation demonstrate the presence of a pharmacodynamic interaction between clopidogrel and omeprazole when administered concomitantly as well as staggered. Given the presence of a pharmacodynamic interaction between omeprazole and clopidogrel irrespective of the timing of their administration, use of omeprazole should be avoided in clopidogreltreated patients.