What are the recommended doses of antiplatelet agents (aspirin and P2Y12 inhibitors) and anticoagulation (unfractionated heparin or low‑molecular‑weight heparin) after thrombolysis in a patient with ST‑elevation myocardial infarction?

Antiplatelet and Anticoagulation Dosing After Thrombolysis in STEMI

After fibrinolytic therapy for STEMI, continue aspirin 81-325 mg daily indefinitely (with 81 mg preferred), add clopidogrel 75 mg daily if already loaded or give a 300-600 mg loading dose depending on PCI timing, and maintain unfractionated heparin or enoxaparin through any subsequent PCI procedure. 1

Aspirin Dosing

• Loading dose: 162-325 mg should be given immediately with the fibrinolytic agent before any PCI 1
• Maintenance dose: 81-325 mg daily continued indefinitely after thrombolysis 1
• Preferred maintenance dose: 81 mg daily is the preferred long-term dose over higher maintenance doses 1

P2Y12 Inhibitor (Clopidogrel) Dosing

The dosing strategy depends critically on whether the patient received clopidogrel with fibrinolysis and the timing of any subsequent PCI:

If Patient Already Received Clopidogrel Loading with Fibrinolysis:

• Continue clopidogrel 75 mg daily without an additional loading dose 1

If No Prior Clopidogrel Loading Dose:

For PCI ≤24 hours after fibrinolysis:

• Give clopidogrel 300 mg loading dose before or at the time of PCI 1

For PCI >24 hours after fibrinolysis:

• Give clopidogrel 600 mg loading dose before or at the time of PCI 1

Maintenance Therapy:

• Clopidogrel 75 mg daily after PCI 1
• Duration: At least 12 months for drug-eluting stents; at least 30 days and up to 12 months for bare-metal stents 1

Prasugrel as Alternative P2Y12 Inhibitor

• Loading dose: 60 mg at the time of PCI, but only if >24 hours after fibrin-specific agent or >48 hours after non-fibrin-specific agent 1
• Maintenance dose: 10 mg daily 1
• Absolute contraindication: Patients with prior stroke or TIA (Class III: Harm) 1

Anticoagulation Dosing

Unfractionated Heparin (UFH):

• Continue UFH through PCI with additional IV boluses as needed to maintain therapeutic activated clotting time (ACT) 1
• Dosing adjustments depend on whether GP IIb/IIIa receptor antagonists are used 1

Enoxaparin (Low-Molecular-Weight Heparin):

• Continue enoxaparin through PCI with the following dosing algorithm 1:
  • No additional drug if last dose was within previous 8 hours
  • 0.3 mg/kg IV bolus if last dose was 8-12 hours earlier
• Enoxaparin is superior to UFH in reducing death or recurrent MI (9.9% vs 12.0%, p<0.001) with increased major bleeding (2.1% vs 1.4%, p<0.001) but favorable net clinical benefit 2

Fondaparinux:

• Class III: Harm - Should not be used as sole anticoagulant for PCI due to risk of catheter thrombosis 1
• An additional anticoagulant with anti-IIa activity must be administered if fondaparinux was used 1

Critical Pitfalls and Caveats

GP IIb/IIIa Inhibitors:

• Should be used with great caution, if at all, after full-dose fibrinolytic therapy due to high rates of bleeding and intracranial hemorrhage, particularly in elderly patients 1

Timing Considerations:

• The 24-hour threshold for clopidogrel loading dose (300 mg vs 600 mg) is critical for balancing efficacy and bleeding risk 1
• Prasugrel must not be given within 24 hours of fibrin-specific fibrinolysis due to excessive bleeding risk 3

Duration of Therapy:

• Premature discontinuation of P2Y12 inhibitors significantly increases stent thrombosis risk 4, 5
• Minimum 12-month dual antiplatelet therapy is essential for patients receiving stents 1, 4

Anticoagulation Selection:

• Enoxaparin provides more stable anticoagulation than UFH with less monitoring required, making it preferable for extended in-hospital use 6, 2
• The superior efficacy of enoxaparin (17% relative risk reduction in death/MI) must be weighed against increased major bleeding 2