Proton-pump inhibitors are endorsed for clopidogrel patients at high risk for gastrointestinal bleeding.
To address the somewhat confusing literature on the interaction between proton-pump inhibitors (PPIs) and clopidogrel, a new "consensus document" has been published jointly by the American College of Cardiology, American College of Gastroenterology, and American Heart Association.
Clopidogrel is converted to its active form by the hepatic enzyme CYP2C19, which is competitively inhibited by PPIs. Although platelet function studies have shown that PPI use lessens clopidogrel-mediated inhibition of platelet aggregation, the clinical relevance of this observation has been debated.
The consensus writers make the following points:
- Some, but not all, observational studies have shown small statistically significant higher risk for adverse cardiovascular events among patients who received PPIs and clopidogrel concomitantly (compared with clopidogrel alone). However, in the only large randomized trial (the recently published COGENT study; JW Cardiol Oct 6 2010), patients who received omeprazole plus clopidogrel had similar rates of adverse cardiovascular events and lower rates of adverse gastrointestinal (GI) events than recipients of clopidogrel alone.
- In patients with histories of upper GI bleeding and those at high risk for this complication (e.g., advanced age; concomitant use of warfarin, steroids, or nonsteroidal anti-inflammatory drugs; Helicobacter pylori infection), the benefits of PPI therapy probably outweigh the very small risk that PPI therapy will interfere with clopidogrel's efficacy.
- Patients at low risk for GI bleeding who require clopidogrel therapy should not receive concomitant PPIs.
This document will disappoint readers who expect an unambiguous algorithm that is easily applied to all patients. Nevertheless, by endorsing use of PPIs for clopidogrel-treated patients at high risk for upper GI bleeding, the authors provide validation for this widespread practice.
Allan S. Brett, MD
Published in Journal Watch General Medicine December 9, 2010
Citation(s): Abraham NS et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: A focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. J Am Coll Cardiol 2010 Dec 7; 56:2051. (http://dx.doi.org/10.1016/j.jacc.2010.09.010)