In a patient with non‑ST‑segment elevation myocardial infarction who has active bleeding that makes aspirin unsafe, what antithrombotic regimen should be used?

Management of NSTEMI with Active Bleeding When Aspirin is Contraindicated

When aspirin is contraindicated due to active bleeding in a patient with NSTEMI, you should use a P2Y12 inhibitor alone—specifically clopidogrel (300-600 mg loading dose, then 75 mg daily), ticagrelor (180 mg loading dose, then 90 mg twice daily), or prasugrel (60 mg loading dose, then 10 mg daily if undergoing PCI)—as monotherapy until the bleeding is controlled. 1

Initial Antithrombotic Strategy During Active Bleeding

P2Y12 Inhibitor Monotherapy

• Clopidogrel is the preferred P2Y12 inhibitor when aspirin cannot be given due to active bleeding, as it has the most favorable bleeding profile among the P2Y12 inhibitors. 1, 2
• Ticagrelor (180 mg loading dose, 90 mg twice daily) is an alternative option for patients unable to take aspirin, though it carries higher bleeding risk than clopidogrel. 1
• Prasugrel (60 mg loading dose, 10 mg daily) can be used in PCI-treated patients who cannot take aspirin, but prasugrel is absolutely contraindicated if the patient has active pathological bleeding. 1

Critical Contraindications to Note

• Do not use prasugrel in patients with active pathological bleeding—this is an absolute contraindication that supersedes its use as aspirin alternative. 1
• All parenteral anticoagulants (unfractionated heparin, low-molecular-weight heparin, fondaparinux) should be discontinued during active bleeding. 2

Timing of Invasive Strategy

High-Risk Features Requiring Early Intervention

• For high-risk NSTEMI patients (hemodynamic instability, refractory ischemia, electrical instability, elevated cardiac biomarkers), proceed with early invasive strategy within 24 hours after hemodynamic stabilization and control of bleeding. 1, 2
• The GRACE score should be used to stratify cardiac risk and determine optimal timing of intervention. 2

Balancing Thrombotic vs. Bleeding Risk

• The decision to proceed with angiography should weigh the severity of both the NSTEMI and the gastrointestinal bleeding, with consideration of the patient's overall risk profile. 2
• Avoid prolonged delay in coronary intervention, as "cooling-off" strategies for 3-5 days do not improve outcomes in high-risk patients. 2

Resuming Dual Antiplatelet Therapy

When to Restart Aspirin

• Restart aspirin at low dose (81 mg daily) as soon as the risk of cardiac events outweighs the risk of recurrent bleeding—this typically occurs after endoscopic control of bleeding or when bleeding has definitively stopped. 2, 3
• Low-dose aspirin (81 mg) has the most favorable risk-benefit profile and should be preferred over higher doses (325 mg) to minimize bleeding risk. 1, 2

Loading Dose Considerations

• When restarting a P2Y12 inhibitor after temporary discontinuation, give a loading dose: clopidogrel 300-600 mg, ticagrelor 180 mg, or prasugrel 60 mg (if PCI performed). 2

Gastroprotection Strategy

Proton Pump Inhibitor Therapy

• Initiate a proton pump inhibitor immediately in all patients requiring antithrombotic therapy after gastrointestinal bleeding—this is a Class I recommendation. 1, 2, 4
• Continue PPI therapy indefinitely as long as the patient remains on antiplatelet or anticoagulant therapy, as history of upper GI bleeding is the strongest predictor of recurrence. 4
• Standard once-daily dosing (e.g., pantoprazole 40 mg daily, omeprazole 20 mg daily) is appropriate for most patients. 4

Long-Term Management After Bleeding Control

Duration of Dual Antiplatelet Therapy

• After bleeding is controlled and aspirin is restarted, continue dual antiplatelet therapy (aspirin plus P2Y12 inhibitor) for at least 12 months in patients receiving drug-eluting stents, unless bleeding risk outweighs benefit. 1
• For patients managed medically without stenting, continue dual antiplatelet therapy for up to 12 months. 1

Dose Adjustments for Special Populations

• In patients weighing <60 kg, consider reducing prasugrel maintenance dose to 5 mg daily due to increased bleeding risk. 1
• In patients ≥75 years old, prasugrel is generally not recommended due to increased risk of fatal and intracranial bleeding, except in high-risk situations (diabetes or prior MI). 1

Common Pitfalls to Avoid

• Do not withhold all antithrombotic therapy—even with active bleeding, P2Y12 inhibitor monotherapy should be continued to prevent stent thrombosis and recurrent MI. 1, 2
• Do not use prasugrel in patients with active bleeding—this is an absolute contraindication that many clinicians overlook. 1
• Do not delay PPI initiation—start gastroprotection immediately, not after bleeding recurs. 2, 4
• Do not use higher-dose aspirin (325 mg) when restarting—81 mg daily provides equivalent efficacy with lower bleeding risk. 1, 2, 3
• Do not forget to document the specific indication for continued PPI therapy in the medical record, as this affects long-term management decisions. 4