What is the management for a patient with a gastrointestinal (GI) bleed on prasugrel (prasugrel) and aspirin (acetylsalicylic acid, ASA)?

Management of GI Bleeding on Prasugrel and ASA

For a patient with active GI bleeding on prasugrel and aspirin, continue aspirin without interruption and temporarily withhold prasugrel during the active bleeding episode, then resume prasugrel within 5 days after achieving endoscopic hemostasis. 1, 2

Initial Antiplatelet Management During Active Bleeding

• Never discontinue both antiplatelet agents simultaneously due to the high risk of stent thrombosis, which can occur in as little as 7 days when both drugs are withheld 1, 2

• Continue aspirin throughout the bleeding episode without interruption, especially if the patient is on aspirin for secondary prevention (history of MI, stroke, or established coronary artery disease) 1, 2, 3

• Temporarily withhold prasugrel during active bleeding to reduce bleeding risk while maintaining some antiplatelet coverage with aspirin 1, 2, 3

• Discontinuation of aspirin for secondary prevention is associated with a nearly sevenfold increase in risk for death or acute cardiovascular events 1, 2

• All-cause mortality is 10 times lower in patients who resume aspirin immediately after endoscopic hemostasis compared to those who discontinue it 1, 2

Resuscitation and Supportive Care

• Initiate high-dose proton pump inhibitor (PPI) therapy immediately for all patients with GI bleeding on antiplatelet therapy 2, 3

• Avoid platelet transfusions in patients on antiplatelet therapy with GI bleeding, as they have not been shown to reduce rebleeding and may be associated with higher mortality 2

• Perform urgent endoscopy for diagnosis and treatment of the bleeding source, as endoscopic hemostasis can be successfully achieved in >95% of cases even in anticoagulated patients 1

Timing of Prasugrel Resumption After Hemostasis

• Resume prasugrel within 5 days after achieving endoscopic hemostasis 1, 2, 3

• For prasugrel specifically, resumption can be delayed up to 5 days after endoscopic hemostasis, which is slightly longer than ticagrelor (2-3 days) due to prasugrel's pharmacokinetic profile 1

• The decision to resume prasugrel should be made in consultation with the patient's cardiologist, particularly if the patient had acute coronary syndrome within 6 months 1

Risk Stratification for Decision-Making

Very high thrombotic risk scenarios requiring continued dual antiplatelet therapy include: 1, 3

• Acute coronary syndrome or percutaneous coronary intervention within 6 weeks
• Drug-eluting stent placed within 6 months
• Left main coronary artery stenting
• Proximal left anterior descending (LAD) artery stenting
• Last remaining patent coronary artery
• Multiple stents or long stent length
• History of stent thrombosis

Risk factors that increase GI bleeding risk include: 4

• Advanced age (≥75 years)
• Body weight <60 kg
• History of peptic ulcer disease or previous GI bleeding
• Concomitant use of anticoagulants, NSAIDs, or corticosteroids
• Helicobacter pylori infection
• Cardiogenic shock

Prasugrel-Specific Bleeding Considerations

• Prasugrel increases major bleeding from 1.8% to 2.4% and fatal bleeding from 0.1% to 0.4% compared to clopidogrel 4

• Prasugrel is generally not recommended in patients ≥75 years due to increased bleeding risk (including fatal bleeding), except in high-risk situations such as patients with diabetes or history of MI 5

• Consider a lower maintenance dose (5 mg instead of 10 mg) for patients with body weight <60 kg 5

• If CABG is required, prasugrel should be discontinued at least 7 days prior to surgery due to significantly increased CABG-related bleeding (14.1% vs 4.5% with clopidogrel) 5

Long-Term GI Protection Strategies

• Continue PPI therapy for the duration of dual antiplatelet therapy to prevent recurrent GI bleeding 1, 2, 3

• Test for and eradicate Helicobacter pylori infection if present 6, 7

• Avoid concomitant NSAIDs, which significantly increase GI bleeding risk when combined with dual antiplatelet therapy 4, 6, 7

• Be aware of potential drug-drug interactions between PPIs and clopidogrel (though this is less relevant for prasugrel, which is not significantly affected by CYP2C19 polymorphisms) 1, 3

Common Pitfalls to Avoid

• Do not unnecessarily prolong discontinuation of antiplatelet therapy, especially aspirin for secondary prevention, as this dramatically increases thrombotic risk and mortality 1, 2, 3

• Do not simultaneously discontinue both aspirin and prasugrel in patients on dual antiplatelet therapy, as stent thrombosis can occur within 7 days 1, 2, 3

• Do not administer platelet transfusions for GI bleeding in patients on antiplatelet therapy, as this may worsen outcomes 2

• Do not restart prasugrel before achieving endoscopic hemostasis, as this may precipitate rebleeding 1, 2

• Do not forget to consult cardiology before making changes to antiplatelet therapy in high-risk patients, particularly those with recent ACS or coronary stents 1