CLOPIDOGREL TAB
Clinical Criteria Summary
Criteria for Clopidogrel TAB
- Mechanism & Pharmacokinetics
- Prodrug requiring biotransformation to active metabolite via hepatic cytochrome P450 (CYP) 2C19 enzyme, which is the same metabolic pathway used by proton pump inhibitors (PPIs).
- Clinical Indications & Use Criteria
- Used as single antiplatelet therapy (SAPT) or in combination with aspirin as dual antiplatelet therapy (DAPT).
- When combined with aspirin therapy, promotes gastric ulcer bleeding and increases risk of gastrointestinal bleeding.
Criteria for Omeprazole (All Formulations)
- Clinical Indications & Use Criteria
- Indicated for patients with GERD who have LA grade C or D esophagitis or whose GERD symptoms are not adequately controlled with alternative medical therapies.
- Indicated for patients receiving any antithrombotic regimen who are at high risk of gastrointestinal bleeding.
- Management & Deprescribing Recommendations
- Recommend deprescribing according to the 2022 ACG Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors as much as possible.
Criteria for Concomitant Use of Clopidogrel TAB and Omeprazole (All Formulations)
- Mechanism & Interaction Considerations
- Concurrent administration may theoretically result in competitive inhibition, potentially decreasing concentration of the active clopidogrel moiety and resulting in decreased effect on platelet aggregation factors.
- PPIs that inhibit CYP2C19, particularly omeprazole and esomeprazole, may reduce the pharmacodynamic response to clopidogrel.
- Safety & Clinical Evidence Criteria
- FDA prescribing information states to avoid concomitant use of clopidogrel with omeprazole or esomeprazole.
- Concomitant use is correlated with increased CV event risk in meta-analyses combining observational cohorts and RCTs; however, significance of this correlation is lost when evaluation is limited to RCTs and propensity score matching (PSM) of observational cohorts.
- No strong evidence that CYP2C19-inhibiting PPIs result in increased risk of ischemic events or stent thrombosis in clinical trials and propensity score-matched studies.
- Use of PPIs is associated with reduced risk of gastrointestinal bleeding in patients treated with DAPT after PCI, with no significant differences observed in incidence of MACE, MI, and all-cause death in patients with CAD on DAPT and PPIs.
- VA Practice Recommendations
- Do not limit omeprazole use in patients on clopidogrel given the lack of adverse cardiovascular effects outlined in recent guidelines.
- For patients meeting GERD or high GI bleeding risk criteria, established benefits of PPI treatment outweigh proposed but highly questionable cardiovascular risks.
- No interaction observed between concomitant use of PPIs and aspirin, prasugrel, or ticagrelor.