New Recommendations Address Use of Clopidogrel, PPIs in High-Risk Patients

The American College of Cardiology, the American College of Gastroenterology, and the American Heart Association have issued consensus recommendations on when physicians should prescribe proton pump inhibitors (PPIs) in addition to clopidogrel. According to an article published in the Journal of the American College of Cardiology, the societies recommend the use of both therapies in high-risk patients, defined as those with a history of upper GI bleeding; those who are elderly or have Helicobacter pylori infections; or those on steroids, warfarin or NSAIDs.

In a previous document, use of PPI was recommended in patients with risk factors for upper GI bleeding treated with dual antiplatelet therapy. Since its publication, evidence of a potential adverse drug interaction between PPIs and thienopyridines has emerged. However, “it has been difficult for practitioners to assimilate this flood of information and to develop optimal treatment strategies for managing patients who might benefit from antiplatelet therapy, yet who might suffer from GI bleeding.”

The goal of the new report is to provide provisional guidance for clinical management, and highlight areas of future research necessary to address current knowledge gaps, the authors wrote.

Key findings from the recommendations are as follows:

1. Clopidogrel reduces major cardiovascular (CV) disease events compared with placebo or aspirin.
2. Dual antiplatelet therapy with clopidogrel and aspirin, compared with aspirin alone, reduces major CV events in patients with established ischemic heart disease, and it reduces coronary stent thrombosis but is not routinely recommended for patients with prior ischemic stroke because of the risk of bleeding.
3. Clopidogrel alone, aspirin alone, and their combination are all associated with increased risk of GI bleeding.
4. Patients with prior GI bleeding are at highest risk for recurrent bleeding on antiplatelet therapy. Other clinical characteristics that increase the risk of GI bleeding include advanced age; concurrent use of anticoagulants, steroids, or nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin; and Helicobacter pylori infection. The risk of GI bleeding increases as the number of risk factors increases.
5. Use of a PPI or histamine H2 receptor antagonist (H2RA) reduces the risk of upper GI bleeding compared with no therapy. PPIs reduce upper GI bleeding to a greater degree than do H2RAs.
6. PPIs are recommended to reduce GI bleeding among patients with a history of upper GI bleeding. PPIs are appropriate in patients with multiple risk factors for GI bleeding who require antiplatelet therapy.
7. Routine use of either a PPI or an H2RA is not recommended for patients at lower risk of upper GI bleeding, who have much less potential to benefit from prophylactic therapy.
8. Clinical decisions regarding concomitant use of PPIs and thienopyridines must balance overall risks and benefits, considering both CV and GI complications.
9. Pharmacokinetic and pharmacodynamic studies, using platelet assays as surrogate endpoints, suggest that concomitant use of clopidogrel and a PPI reduces the antiplatelet effects of clopidogrel. The strongest evidence for an interaction is between omeprazole and clopidogrel. It is not established that changes in these surrogate endpoints translate into clinically meaningful differences.
10. Observational studies and a single randomized clinical trial (RCT) have shown inconsistent effects on CV outcomes of concomitant use of thienopyridines and PPIs. A clinically important interaction cannot be excluded, particularly in certain subgroups, such as poor metabolizers of clopidogrel.
11. The role of either pharmacogenomic testing or platelet function testing in managing therapy with thienopyridines and PPIs has not yet been established.

To read the recommendations, click here.