Perspective:

The following are 10 points to remember about this position paper:

1. This document reviews the pharmacokinetic background of the interactions between clopidogrel and proton pump inhibitors (PPIs), and their consequences on clinical outcomes, and presents suggestions for management of this important issue.

2. So far, there are insufficient data to suggest a clinical interaction between PPI use and the protective efficacy of aspirin in patients with cardiovascular disease. Use of PPIs is recommended for the prevention of gastric ulceration in aspirin-treated patients at high risk of gastrointestinal (GI) bleeding.

3. Potential negative clinical impacts of some PPIs on the therapeutic efficacy of clopidogrel are still controversial.

4. In view of the pharmacokinetic data and inconclusive clinical evidence, PPIs with weaker inhibition of CYP2C19 such as pantoprazole are preferred in combination with clopidogrel compared with those with stronger inhibition such as omeprazole.

5. Current data do not support the need to avoid concomitant use of PPIs, when clinically indicated, in patients receiving prasugrel.

6. There is no evidence of any adverse interaction between ticagrelor and PPIs. The use of PPIs is recommended in ticagrelor-treated patients who are at an increased risk of GI hemorrhage.

7. PPIs may accelerate absorption of warfarin, and omeprazole may influence vitamin K antagonists (VKAs)’ pharmacokinetics more than newer PPIs. At present, it is appropriate to monitor cautiously patients on VKA and PPI co-medication.

8. PPIs may be useful to alleviate dyspepsia related to dabigatran as well as reduce GI bleeding risk. Current evidence indicates that the mild reduction in dabigatran exposure related to PPI usage does not warrant any dose adjustment.

9. The administration of PPIs to patients receiving oral factor Xa inhibitory drugs is unlikely to influence the pharmacokinetics of the drugs and is warranted if an increased risk of GI bleeding is expected.

10. Given the large number of patients treated with PPIs and antithrombotic drugs, even a minor reduction in the cardiovascular benefits of antithrombotic drugs may have substantial clinical impact. Accordingly, more studies are needed to elucidate the clinical importance of the drug interactions described in this position paper.