Should a patient on antiplatelet therapy, specifically clopidogrel (Plavix), be discharged with a proton pump inhibitor (PPI), such as omeprazole (Prilosec), to prevent gastrointestinal bleeding?

Proton Pump Inhibitor Use in Patients on Antiplatelet Therapy

Yes, patients on clopidogrel (Plavix) should be discharged with a proton pump inhibitor (PPI) to prevent gastrointestinal bleeding, especially those with risk factors for GI bleeding. 1, 2

Rationale for PPI Co-Prescription

• PPIs are often prescribed prophylactically when clopidogrel is started to prevent gastrointestinal complications such as ulceration and related bleeding due to dual antiplatelet therapy, particularly when combined with aspirin 1
• Dual antiplatelet therapy has been shown to increase the risk of gastrointestinal bleeding up to 2-fold, especially in patients with multiple risk factors 3
• Prophylactic use of a PPI has been demonstrated to reduce the rate of upper gastrointestinal bleeding in patients receiving aspirin and clopidogrel 4

Risk Factors That Strengthen the Indication for PPI

Patients should receive PPI therapy with clopidogrel if they have any of the following risk factors:

• Prior history of upper GI bleeding 1, 3
• Advanced age 1, 5
• Concomitant use of warfarin 5
• Concomitant use of steroids or non-steroidal anti-inflammatory drugs 3, 5
• Helicobacter pylori infection 5

Concerns About PPI-Clopidogrel Interaction

• PPIs have been found to interfere with the metabolism of clopidogrel through inhibition of CYP2C19 1
• There have been retrospective reports of adverse cardiovascular outcomes when clopidogrel and aspirin are accompanied by PPIs 1
• However, the only randomized controlled trial examining this interaction (COGENT) found no significant difference in cardiovascular events between patients taking omeprazole with clopidogrel versus clopidogrel alone (HR: 0.99; 95% CI: 0.68 to 1.44) 1, 4

Choice of PPI

• If a PPI is indicated, consider using pantoprazole rather than omeprazole or esomeprazole 6, 7
• Some studies have suggested that pantoprazole may have less effect on CYP2C19 and therefore less interaction with clopidogrel 1, 6
• The FDA label for clopidogrel specifically warns against concomitant use of omeprazole or esomeprazole 7

Clinical Algorithm for PPI Use with Clopidogrel

1. Assess patient's risk for GI bleeding:

   • If patient has any risk factors (prior GI bleed, advanced age, concomitant anticoagulants or NSAIDs, H. pylori infection), prescribe a PPI 1, 3
   • If no risk factors are present, PPI prophylaxis may not be necessary 3

2. If PPI is indicated, select the appropriate agent:

   • Prefer pantoprazole over omeprazole/esomeprazole due to less CYP2C19 inhibition 6, 5
   • Avoid omeprazole and esomeprazole if possible, as specifically warned against in the clopidogrel FDA label 7

3. Consider timing of administration:

   • Some evidence suggests that separating the timing of clopidogrel and PPI administration by 12 hours may minimize potential interactions 1

Monitoring Recommendations

• Monitor for signs of GI bleeding (melena, hematemesis, anemia) 1
• Be vigilant for cardiovascular events, although current evidence suggests the risk is not significantly increased with concomitant PPI use 4, 8
• Consider platelet function testing in high-risk patients if available, though routine testing is not recommended 8

In conclusion, the benefits of PPI therapy in preventing GI bleeding in patients on antiplatelet therapy outweigh the theoretical concerns about reduced clopidogrel efficacy, particularly in patients with risk factors for GI bleeding 1, 4.