What is the management of gastrointestinal bleeding in patients on antiplatelet therapy with aspirin (acetylsalicylic acid) alone or aspirin plus clopidogrel?

From the Guidelines

For patients with active GI bleeding on aspirin alone or aspirin plus clopidogrel, the management involves temporarily discontinuing clopidogrel while continuing aspirin, as this approach delays the onset of coronary events and minimizes the risk of bleeding, as recommended by the joint Asian Pacific Association of Gastroenterology (APAGE) and Asian Pacific Society for Digestive Endoscopy (APSDE) practice guidelines 1.

Management Approach

The management of gastrointestinal bleeding in patients on antiplatelet therapy with aspirin alone or aspirin plus clopidogrel requires a balanced approach to control bleeding while considering thrombotic risks.

• Endoscopic intervention should be performed within 24 hours to identify and treat the bleeding source.
• Proton pump inhibitors (PPIs) should be administered intravenously for the first 72 hours, followed by oral PPI therapy.
• Blood transfusions should be given to maintain hemoglobin above 7 g/dL (or 8-9 g/dL in patients with cardiovascular disease).

Resuming Antiplatelet Therapy

The decision to resume antiplatelet therapy depends on the indication and bleeding risk.

• For patients with high thrombotic risk (recent coronary stents, especially drug-eluting stents placed within 6 months, or bare metal stents within 1 month), aspirin should be continued, and clopidogrel may be resumed within 5-7 days after bleeding is controlled, as suggested by the British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines 1.
• For lower-risk indications, antiplatelet therapy can be withheld longer (7-10 days).

Considerations

Upon resumption, concurrent PPI therapy should be continued indefinitely to reduce rebleeding risk, as recommended by the American College of Cardiology Foundation Task Force on Expert Consensus Documents 1. This approach balances the competing risks of recurrent bleeding against thrombotic events, as premature discontinuation of dual antiplatelet therapy carries significant cardiovascular risks, particularly in patients with recent stent placement, as highlighted in a study published in Gut 1.

From the FDA Drug Label

Because the half-life of clopidogrel’s active metabolite is short, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 4 hours of the loading dose or 2 hours of the maintenance dose may be less effective Discontinuation of clopidogrel tablets increases the risk of cardiovascular events. If clopidogrel tablets must be temporarily discontinued (e.g., to treat bleeding or for surgery with a major risk of bleeding), restart it as soon as possible. In CURE, clopidogrel tablets use with aspirin was associated with an increase in major bleeding (primarily gastrointestinal and at puncture sites) compared to placebo with aspirin CAPRIE(Clopidogrel vs Aspirin) In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2.0% in those taking clopidogrel tablets versus 2.7% in those taking aspirin;

The management of gastrointestinal bleeding in patients on antiplatelet therapy with aspirin alone or aspirin plus clopidogrel involves:

• Discontinuing the antiplatelet therapy if possible, to reduce the risk of further bleeding
• Administering exogenous platelets to restore hemostasis, although this may be less effective if done shortly after a dose of clopidogrel
• Restarting antiplatelet therapy as soon as possible after the bleeding has been controlled, to minimize the risk of cardiovascular events
• Monitoring for signs of bleeding and being aware of the potential for increased bleeding risk with concomitant use of strong CYP2C19 inducers 2 Key considerations:
• The risk of bleeding is increased with the use of clopidogrel and aspirin, particularly gastrointestinal bleeding
• Discontinuation of antiplatelet therapy increases the risk of cardiovascular events
• Platelet transfusions may be used to restore hemostasis, but their effectiveness may be reduced if done shortly after a dose of clopidogrel Main points:
• Discontinue antiplatelet therapy if possible to reduce bleeding risk
• Administer exogenous platelets to restore hemostasis
• Restart antiplatelet therapy as soon as possible after bleeding is controlled
• Monitor for signs of bleeding and be aware of potential interactions with other medications 2

From the Research

Management of Gastrointestinal Bleeding in Patients on Antiplatelet Therapy

The management of gastrointestinal bleeding in patients on antiplatelet therapy with aspirin alone or aspirin plus clopidogrel involves several considerations.

• For patients on aspirin alone, the use of proton pump inhibitors (PPIs) has been shown to decrease the rate of upper gastrointestinal bleeding 3.
• In patients receiving clopidogrel, the combination of aspirin and clopidogrel increases the risk of upper gastrointestinal bleeding 3.
• The use of PPIs in patients on clopidogrel is more complex, with some studies suggesting a decreased antiplatelet effect of clopidogrel when co-administered with PPIs, particularly those with high CYP2C19 inhibiting activity such as omeprazole and esomeprazole 4, 5.
• However, other studies have found that the combination of aspirin and a PPI is associated with a reduced risk of recurrent hospitalization for major gastrointestinal complications, whereas the combination of clopidogrel and a PPI is not 6.

Specific Considerations for Aspirin Alone or Aspirin Plus Clopidogrel

• For patients on aspirin alone, the addition of a PPI may be beneficial in reducing the risk of gastrointestinal bleeding, particularly in those at high risk of bleeding 3, 6.
• For patients on aspirin plus clopidogrel, the management of gastrointestinal bleeding is more complex, and the decision to use a PPI should be made on a case-by-case basis, taking into account the individual patient's risk of bleeding and cardiovascular events 4, 3, 7.
• In some cases, the discontinuation of dual antiplatelet therapy and the use of single antiplatelet therapy with aspirin may be necessary to manage gastrointestinal bleeding, as seen in a case report of a patient with a large duodenal gastrointestinal stromal tumor 7.