What is the recommended management for antiplatelet therapy in a patient with a history of upper gastrointestinal bleeding due to a perforated duodenal ulcer, who is at risk for stroke and requires anticoagulation therapy, and was previously on antiplatelet therapy for secondary prevention of cardiovascular events?

Antiplatelet Management After Upper GI Bleeding from Perforated Duodenal Ulcer

In patients requiring antiplatelet therapy for secondary cardiovascular prevention who develop upper GI bleeding from a perforated duodenal ulcer, aspirin should be restarted as soon as the cardiovascular risk outweighs the bleeding risk—typically immediately after endoscopic hemostasis is achieved—and must be combined with high-dose PPI therapy. 1

Timing of Antiplatelet Resumption

The decision to restart aspirin hinges on cardiovascular risk stratification, not arbitrary waiting periods. 1, 2

• For patients with high cardiovascular risk (recent acute coronary syndrome, recent stroke, or recent percutaneous coronary intervention with stents), aspirin should be restarted immediately after endoscopic control of bleeding is achieved. 1

• No aspirin-free period should be mandated when cardiovascular risk is high, as discontinuation increases thrombotic risk substantially. 1, 2

• Discontinuing aspirin is associated with a 3-fold higher risk of major adverse cardiac events, with thrombotic events typically occurring 7-10 days after cessation. 1, 2

• A randomized trial demonstrated that immediate aspirin resumption (with PPI therapy) resulted in 10-fold lower all-cause mortality (1.7% vs 14.5%) compared to withholding aspirin, despite a numerically higher but non-significant rebleeding rate (18.9% vs 10.9%). 1

Critical Caveat About Rebleeding Risk

• Early aspirin resumption does carry a numerical trend toward higher rebleeding rates (approximately 19% vs 11%), though this did not reach statistical significance in the pivotal trial. 1

• PPI therapy alone cannot completely eliminate aspirin-induced rebleeding risk, as antiplatelet drugs impair platelet-plug formation even in the presence of acid suppression. 1

• This rebleeding risk must be weighed against the significantly higher mortality from cardiovascular events when aspirin is withheld. 1

Mandatory Concurrent PPI Therapy

Restarting aspirin without PPI co-therapy is a critical error that substantially increases rebleeding risk. 1, 2

• After endoscopic hemostasis, administer high-dose PPI therapy via intravenous loading dose followed by continuous infusion for 72 hours. 1, 3

• Following the initial 3-day IV infusion, continue oral PPI twice daily for 14 days, then once daily for a duration dictated by the underlying ulcer etiology (typically 4-6 weeks for duodenal ulcers). 1, 2

• Long-term PPI therapy is recommended for all patients requiring continued single or dual antiplatelet therapy after previous ulcer bleeding. 1, 3

Management of Dual Antiplatelet Therapy (DAPT)

For patients on dual antiplatelet therapy (aspirin plus P2Y12 inhibitor like clopidogrel), management requires cardiology consultation to balance stent thrombosis risk against rebleeding risk. 1, 2

• Aspirin should generally be continued even in patients on DAPT, as it provides the foundation of antiplatelet protection. 2, 4

• P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) should be restarted within 5 days after endoscopic diagnosis if temporarily discontinued. 2

• Never discontinue both antiplatelet agents simultaneously in patients with recent coronary stents, as stent thrombosis can occur within 7 days. 2

• There is no evidence that switching from aspirin to clopidogrel alone reduces bleeding risk in patients with active ulcers. 1

• In fact, aspirin plus PPI is superior to clopidogrel monotherapy for preventing recurrent bleeding (OR 0.06) while maintaining cardiovascular protection. 1, 2

Specific Considerations for Perforated Ulcer

• Surgical consultation is mandatory for perforated duodenal ulcers, as endoscopic therapy alone may be insufficient. 1

• After surgical repair, the same principles apply: restart aspirin as soon as cardiovascular risk outweighs bleeding risk, typically within 24-72 hours post-operatively if hemostasis is secure. 1, 2

• Helicobacter pylori testing and eradication is essential in all patients with peptic ulcer disease, with confirmation of eradication required. 1, 3

Algorithm for Antiplatelet Resumption

1. Assess cardiovascular indication:

   • Secondary prevention (prior MI, stroke, or established cardiovascular disease): High priority for aspirin resumption 2
   • Primary prevention only: Consider permanent discontinuation 2

2. Achieve endoscopic or surgical hemostasis of the perforated ulcer 1

3. Initiate high-dose IV PPI therapy immediately (loading dose followed by continuous infusion) 1, 3

4. For high cardiovascular risk patients:

   • Restart aspirin immediately or within 24 hours after hemostasis 1, 2
   • Continue IV PPI for 72 hours 1, 3

5. Transition to oral PPI twice daily for 14 days, then once daily 1

6. Test and treat H. pylori with confirmation of eradication 1, 3

7. Continue long-term PPI therapy as secondary prophylaxis for all patients on antiplatelet therapy 1, 3

Common Pitfalls to Avoid

• Unnecessarily delaying aspirin resumption increases thrombotic risk and mortality more than it reduces rebleeding risk. 1, 2

• Failing to provide concurrent PPI therapy when restarting aspirin significantly increases rebleeding risk. 1, 2

• Switching to clopidogrel monotherapy without PPI does not reduce bleeding risk and may increase cardiovascular events compared to aspirin plus PPI. 1, 2

• Withholding aspirin for arbitrary time periods (e.g., "wait until ulcer heals") ignores the time-dependent cardiovascular risk. 1, 2

• Inadequate PPI dosing (once daily instead of twice daily initially, or omitting the high-dose IV phase) reduces protection against rebleeding. 1