In a hemodynamically stable patient after successful endoscopic control of an upper gastrointestinal bleed, when and how should antiplatelet therapy (low‑dose aspirin and, if indicated, clopidogrel) be resumed, including timing for dual therapy and use of a proton‑pump inhibitor?

Antiplatelet Management After Upper GI Bleeding

Immediate Resumption for Secondary Prevention

For patients on aspirin for secondary cardiovascular prevention, restart aspirin immediately on the same day that endoscopic hemostasis is confirmed, along with high-dose proton-pump inhibitor therapy. 1, 2

This aggressive approach is justified by compelling mortality data:

• All-cause mortality is reduced ten-fold (1.3% vs 12.9%) when aspirin is resumed immediately after endoscopic hemostasis compared to discontinuation. 1, 2
• Discontinuing aspirin increases the risk of death or acute cardiovascular events nearly seven-fold (HR 6.9), with most thrombotic events occurring 7-10 days after cessation. 1, 2
• The modest numerical increase in rebleeding risk is far outweighed by the dramatic mortality benefit. 1, 2

Primary Prevention: Permanent Discontinuation

Permanently discontinue aspirin in patients using it for primary prevention who experience an upper GI bleed, as bleeding risk outweighs the modest cardiovascular benefit in this population. 2, 3

Dual Antiplatelet Therapy (DAPT) Management

During Active Bleeding

For patients on DAPT with aspirin and clopidogrel, continue aspirin and temporarily withhold only the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor). 1, 2

Never withhold both antiplatelet agents simultaneously—the median time to coronary stent thrombosis can be as short as 7 days when both drugs are stopped, compared to 122 days when only clopidogrel is held. 1, 2

Timing of P2Y12 Inhibitor Resumption

Resume the P2Y12 inhibitor within 5 days maximum after endoscopic hemostasis to prevent stent thrombosis. 1, 2

The specific timing depends on the agent:

• Ticagrelor: Resume within 2-3 days (reversible inhibitor with platelet function returning in 3-5 days). 1, 3
• Clopidogrel or prasugrel: Resume within 5 days (irreversible inhibitors requiring longer recovery). 1

High-Risk Stent Patients

For patients with acute coronary syndrome or percutaneous coronary intervention within 6 months, mandatory cardiology consultation is required before any modification of DAPT. 1, 2

The thrombotic risk stratification is critical:

• Very high risk (ACS or PCI <6 weeks): Defer elective procedures; maintain DAPT if bleeding occurs. 1
• High risk (ACS or PCI 6 weeks to 6 months): Continue aspirin, hold P2Y12 inhibitor briefly, resume within 5 days. 1
• Moderate-low risk (>6 months post-event): Standard DAPT interruption protocol applies. 1

Proton-Pump Inhibitor Co-Therapy

Initiate high-dose PPI therapy immediately when antiplatelet therapy is restarted after an upper GI bleed. 2, 3, 4

Important Drug Interaction Caveat

In Asian patients on clopidogrel with high-dose PPI therapy, be aware that up to 25% are CYP2C19 slow metabolizers (vs <5% in Western populations), which may reduce clopidogrel efficacy through drug-drug interaction. 1

This pharmacogenetic concern provides additional rationale for continuing aspirin while temporarily holding clopidogrel during the acute bleeding phase in Asian patients. 1

Severity-Based Algorithm

Life-Threatening or Massive Bleeding

1. Withhold aspirin temporarily during active resuscitation. 1, 2
2. Achieve endoscopic hemostasis. 1
3. Restart aspirin the same day hemostasis is confirmed. 1, 2
4. Resume P2Y12 inhibitor within 5 days if on DAPT. 1, 2
5. Initiate high-dose PPI concurrently. 2, 4

Non-Life-Threatening Bleeding

Continue aspirin without interruption in patients with high cardiovascular risk (recent ACS or stroke), proceed with urgent endoscopy while maintaining aspirin therapy. 2, 3

Common Pitfalls to Avoid

Unnecessarily delaying aspirin resumption increases thrombotic risk and mortality far more than the risk of rebleeding. 2, 3, 5

Do not administer platelet transfusions to patients on antiplatelet therapy with GI bleeding—this practice does not reduce rebleeding and is associated with higher mortality. 1

Failing to provide concurrent PPI therapy when restarting aspirin significantly increases rebleeding risk. 5, 4

Overlooking the indication for antiplatelet therapy (primary vs secondary prevention) leads to inappropriate management decisions. 2, 3