Key result
Concomitant use of proton pump inhibitors diminishes the antiplatelet effect of clopidogrel, prompting recommendations against routine coadministration and suggesting H2 blockers as an alternative.
Why the study?
Does concomitant use of proton pump inhibitors reduce the antiplatelet effect of clopidogrel, and are H2 blockers a viable alternative for gastrointestinal protection?
Does concomitant use of proton pump inhibitors reduce the antiplatelet effect of clopidogrel, and are H2 blockers a viable alternative for gastrointestinal protection?
Routine coadministration of PPIs and clopidogrel should be avoided due to drug interactions reducing clopidogrel's efficacy; H2 blockers like famotidine offer a safer alternative for GI protection.
Answers are grounded in this paper and cite their sources.
May warrant caution with PPI-clopidogrel co-use; leaves open need for RCTs confirming interaction and H2-blocker alternatives.
Dual antiplatelet therapy with aspirin and clopidogrel is essential after percutaneous coronary intervention. Clopidogrel is a prodrug and requires metabolism by cytochrome p450 enzymes (CYPs), especially CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are metabolized by CYP2C19. Concomitant use of PPI in dual antiplatelet therapy diminishes the antiplatelet effect of clopidogrel, although it is controversial whether its clinical efficacy is reduced. The US FDA and European Medicines Agency recommend that PPIs and clopidogrel should not be coadministered routinely, and the 2010 expert consensus of ACCF/ AGC/ AHA supports this recommendation. On the other hand, histamine receptor type2 (H2) blockers also reduce gastric acid secretion and are used for the treatment of gastroduodenal ulcers. Famotidine, an H2 blocker, has been shown recently to reduce gastric mucosal injury caused by aspirin therapy, although the protective effects of H2 blockers are weaker than that of PPI. Therefore, H2 blockers except cimetidine, which is inactivated by CYP2C19, could be an alternative for PPI in patients treated with clopidogrel, who are at risk of low gastrointestinal tract bleeding.
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Yamane et al. (2011) conducted a review in Patients treated with clopidogrel at risk of gastrointestinal bleeding. Proton pump inhibitors (PPIs) and clopidogrel coadministration vs. H2 blockers was evaluated. Concomitant use of proton pump inhibitors diminishes the antiplatelet effect of clopidogrel, prompting recommendations against routine coadministration and suggesting H2 blockers as an alternative.
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