The Clinical Significance of the Interaction between Proton Pump Inhibitors and Clopidogrel

Abstract

Objective:

To determine whether the interaction between omeprazole and clopidogrel is a proton pump inhibitor (PPI) class effect or a drug-specific effect.

Data Sources:

A MEDLINE search for primary literature was completed (through August 2009) using the search terms proton pump inhibitors and clopidogrel. Additional data obtained from references and abstracts presented at clinical meetings were included when appropriate.

Study Selection:

Nine primary literature articles were identified and reviewed. This included only one prospective, double-blind, placebo-controlled, randomized trial. The remainder were prospective and retrospective cohort studies and a population-based nested case-control study.

Data Extraction:

Omeprazole, a CYP2C19 inhibitor, has been shown to increase the platelet reactivity index (PRI) when combined with clopidogrel (52.4% vs 39.8%; p < 0.0001), leading to an increased risk of thrombosis. This combination was also shown to cause a 25% increase in the risk of mortality or rehospitalization for acute coronary syndrome (ACS), with a significantly higher risk for each 10% increase in time on this combination therapy (odds ratio [OR] 1.07; CI 1.05 to 1.09). Conversely, combination therapy with pantoprazole or esomeprazole and clopidogrel caused a nonsignificant increase in PRI (p = 0.382) and adenosine diphosphate-induced platelet aggregation (p = 0.69 and 0.88, respectively). Similarly, the combination of pantoprazole and clopidogrel was not associated with an increased risk of myocardial infarction (OR 1.02 [0.70–1.47]) when patients were followed for 90 days following hospital discharge for ACS. One study has shown a class effect when PPIs are combined with clopidogrel, leading to an increased risk of a major adverse cardiovascular event (hazard ratio 1.51; 1.39 to 1.64). Histamine₂ (H₂)-receptor antagonists have not been associated with a significant interaction with clopidogrel in any study.

Conclusions:

The use of PPIs with clopidogrel may be warranted, based on comorbid disease states for many patients, but H₂-receptor antagonists should be considered when appropriate, due to their lack of interaction with clopidogrel.