When should loading doses of antiplatelet and anticoagulant medications be administered in the management of myocardial infarction?

When to Administer Loading Doses of Antiplatelet and Anticoagulant Medications in Myocardial Infarction

For STEMI patients undergoing primary PCI, aspirin 162-325 mg should be given immediately before the procedure, and P2Y12 inhibitor loading doses (clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg) should be administered as early as possible or at the time of primary PCI. 1

STEMI Managed with Primary PCI

Antiplatelet Loading Doses

Aspirin:

• Administer 162-325 mg loading dose before primary PCI 1
• This should be given immediately upon STEMI diagnosis, not delayed until catheterization 1

P2Y12 Inhibitors - Timing Based on Clinical Scenario:

For STEMI presenting within 12 hours of symptom onset:

• Loading dose can be given at time of diagnosis, though most patients receive it at time of PCI 2
• Options include clopidogrel 600 mg, prasugrel 60 mg, or ticagrelor 180 mg as early as possible or at time of primary PCI 1

For UA/NSTEMI or STEMI presenting >12 hours after symptom onset:

• The prasugrel FDA label specifically states the loading dose should not be administered until coronary anatomy is established 2
• This approach balances efficacy against bleeding risk in patients who may require urgent CABG 2
• Clopidogrel 600 mg or ticagrelor 180 mg can be given as early as possible or at time of PCI 1

Critical Contraindication:

• Never give prasugrel to patients with prior stroke or TIA - this is a Class III (Harm) recommendation 1

Anticoagulant Administration

Unfractionated Heparin (UFH):

• Administer IV bolus before or at start of PCI 1
• Dosing depends on GP IIb/IIIa inhibitor use:
  • With GP IIb/IIIa planned: 50-70 U/kg bolus 1
  • Without GP IIb/IIIa planned: 70-100 U/kg bolus 1
• Additional boluses given as needed to maintain therapeutic ACT during procedure 1

Bivalirudin:

• 0.75 mg/kg IV bolus, then 1.75 mg/kg/h infusion 1
• Can be given with or without prior UFH treatment 1
• Preferred over UFH with GP IIb/IIIa in high bleeding risk patients 1

STEMI After Fibrinolytic Therapy (Rescue or Delayed PCI)

Antiplatelet Timing

Aspirin:

• 162-325 mg loading dose should already have been given with fibrinolytic agent 1

Clopidogrel - Timing Based on Fibrinolytic Administration:

If already received loading dose with fibrinolytic:

• Continue 75 mg daily without additional loading dose 1

If no prior loading dose:

• PCI ≤24 hours after fibrinolysis: Give 300 mg loading dose before or at time of PCI 1
• PCI >24 hours after fibrinolysis: Give 600 mg loading dose before or at time of PCI 1

Prasugrel:

• Only give if PCI performed >24 hours after fibrin-specific agent or >48 hours after non-fibrin-specific agent 1
• 60 mg loading dose at time of PCI once coronary anatomy known 1
• Must wait at least 24 hours after fibrinolytic to avoid excessive bleeding 1

Anticoagulant Continuation

UFH:

• Continue through PCI with additional IV boluses as needed to maintain therapeutic ACT 1

Enoxaparin:

• Continue through PCI 1
• No additional dose if last dose within 8 hours 1
• Give 0.3 mg/kg IV bolus if last dose 8-12 hours earlier 1

Fondaparinux:

• Never use as sole anticoagulant for PCI - Class III (Harm) recommendation 1
• Must add anticoagulant with anti-IIa activity due to catheter thrombosis risk 1

UA/NSTEMI Management

Early Invasive Strategy

Before Diagnostic Angiography (Upstream Therapy):

• Aspirin 162-325 mg immediately 1, 3
• Clopidogrel loading dose (300-600 mg) before angiography 1, 3
• Alternative: IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban preferred over abciximab unless no delay to angiography and PCI likely) 1
• Anticoagulation with UFH, enoxaparin, fondaparinux, or bivalirudin 1, 3

At Time of PCI (if not given upstream):

• Clopidogrel loading dose if not started before angiography 1
• GP IIb/IIIa inhibitor for troponin-positive and high-risk patients 1

Conservative Strategy

Initial Medical Management:

• Aspirin 162-325 mg immediately 1, 4
• Clopidogrel loading dose (300 mg) as soon as possible after admission 1, 4
• Anticoagulation continued for at least 48 hours or until discharge 1

If Recurrent Ischemia Develops:

• Add GP IIb/IIIa inhibitor (eptifibatide or tirofiban) or give clopidogrel loading dose if not already administered before proceeding to angiography 1

Critical Pitfalls to Avoid

Timing Errors:

• In a trial of 4,033 NSTEMI patients, prasugrel loading dose given before diagnostic angiography showed no clear benefit compared to administration at time of PCI, but increased bleeding risk in patients undergoing PCI or early CABG 2
• Delays in medication administration are common in transfer patients, with median delays of 119 minutes for clopidogrel and 107 minutes for GP IIb/IIIa inhibitors 5

Dosing Errors:

• Transfer patients have higher risk of excess heparin dosing (adjusted OR 1.28 for UFH, 1.54 for LMWH), associated with increased major bleeding 5
• For prasugrel, reduce maintenance dose to 5 mg daily in patients <60 kg due to increased bleeding risk 2

Contraindications:

• Never administer prasugrel to patients with prior stroke/TIA - net harm demonstrated 1, 2
• Avoid prasugrel in patients ≥75 years except high-risk situations (diabetes, prior MI) 2
• Do not use fondaparinux as sole anticoagulant for PCI 1

CABG Considerations:

• If urgent CABG needed, aspirin should not be withheld 1
• Discontinue clopidogrel or ticagrelor at least 24 hours before urgent CABG if possible 1
• Discontinue prasugrel 5-7 days before elective CABG 1
• Risk of significant bleeding is substantial if CABG required after prasugrel loading 2