What are the appropriate loading doses of aspirin, a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel), anticoagulation (unfractionated heparin, enoxaparin, or bivalirudin), and fibrinolytic therapy for an adult with acute myocardial infarction without contraindications?

Loading Doses for Acute Myocardial Infarction

Administer aspirin 162–325 mg (non-enteric-coated, chewable) immediately, followed by a P2Y12 inhibitor loading dose (ticagrelor 180 mg or prasugrel 60 mg preferred; clopidogrel 600 mg if others unavailable), plus anticoagulation with unfractionated heparin (weight-adjusted bolus) or enoxaparin (30 mg IV then 1 mg/kg SC), and fibrinolytic therapy only for STEMI when PCI is delayed >120 minutes.

Aspirin Loading

Immediate administration is critical:

• Give 162–325 mg of non-enteric-coated, chewable aspirin immediately upon ACS recognition 1, 2
• The aspirin must be chewed to achieve fastest antiplatelet effect 2
• Avoid enteric-coated formulations initially—they cause delayed and reduced absorption 1, 2, 3
• Intravenous aspirin (75–250 mg) is acceptable when oral route is unavailable 1
• Rectal administration (325 mg) is an alternative if oral/IV routes are impossible 2

Maintenance dosing:

• Continue aspirin 75–100 mg daily indefinitely 1
• When using ticagrelor, aspirin maintenance must be ≤100 mg daily (81 mg preferred) because higher doses blunt ticagrelor's efficacy 1, 2
• Do not use high-dose aspirin maintenance (≥160 mg)—it increases bleeding without improving outcomes 1, 2

P2Y12 Inhibitor Loading Doses

For STEMI with Primary PCI:

Preferred agents:

• Ticagrelor 180 mg loading dose, then 90 mg twice daily 1
• Prasugrel 60 mg loading dose, then 10 mg daily 1
• Both should be given as early as possible before or at time of PCI 1, 2

Alternative when preferred agents unavailable:

• Clopidogrel 600 mg loading dose (preferred over 300 mg for faster onset), then 75 mg daily 1, 2

For NSTE-ACS with Early Invasive Strategy (angiography ≤24 hours):

• Ticagrelor 180 mg is preferred over clopidogrel for superior efficacy 1, 2
• Prasugrel 60 mg should be given after coronary anatomy is defined at time of PCI—do not give before angiography in NSTE-ACS 1, 2
• Clopidogrel 300–600 mg (600 mg preferred) if ticagrelor/prasugrel contraindicated or unavailable 1

For STEMI with Fibrinolytic Therapy:

Age-specific clopidogrel dosing:

• Age ≤75 years: clopidogrel 300 mg loading dose, then 75 mg daily 1, 3
• Age >75 years: NO loading dose—start directly with clopidogrel 75 mg daily due to bleeding risk 1, 3
• Prasugrel and ticagrelor are not recommended with fibrinolytic therapy 1

Critical Prasugrel Restrictions:

• Contraindicated in patients with prior stroke or TIA (Class III: Harm) 1
• Reduce maintenance dose to 5 mg daily if body weight <60 kg 1, 2
• Generally not recommended in patients ≥75 years except high-risk situations (diabetes, prior MI) 1

Anticoagulation Loading Doses

Unfractionated Heparin (UFH):

For PCI:

• 70–100 IU/kg IV bolus if no GP IIb/IIIa inhibitor planned 1
• 50–70 IU/kg IV bolus if GP IIb/IIIa inhibitor used 1
• Target activated clotting time (ACT) 250–350 seconds without GP IIb/IIIa, or 200–250 seconds with GP IIb/IIIa 1

For fibrinolytic therapy:

• 60 IU/kg IV bolus (maximum 4000 IU), then 12 IU/kg/hour infusion (maximum 1000 IU/hour) 1
• Adjust to maintain aPTT 1.5–2.0 times control (approximately 50–70 seconds) 1
• Continue for 48 hours or until revascularization 1

Enoxaparin:

For PCI (if pre-treated with subcutaneous enoxaparin):

• Additional 0.3 mg/kg IV dose if last subcutaneous dose was 8–12 hours before PCI 1
• Do not "stack" UFH with enoxaparin within 12 hours (Class III: Harm) 1

For fibrinolytic therapy:

• Age ≤75 years: 30 mg IV bolus, then 1 mg/kg SC every 12 hours (maximum 100 mg for first 2 doses) 1
• Age >75 years: NO bolus—give 0.75 mg/kg SC every 12 hours (maximum 75 mg for first 2 doses) 1
• Creatinine clearance <30 mL/min: 1 mg/kg SC every 24 hours regardless of age 1
• Continue for duration of hospitalization, up to 8 days or until revascularization 1

Bivalirudin:

• 0.75 mg/kg IV bolus, then 1.75 mg/kg/hour infusion 1
• Additional 0.3 mg/kg bolus can be given if needed 1
• Reduce infusion to 1 mg/kg/hour if creatinine clearance <30 mL/min 1
• Preferred over UFH with GP IIb/IIIa inhibitor in high bleeding risk patients 1

Fondaparinux:

For fibrinolytic therapy or conservative management:

• 2.5 mg IV initial dose, then 2.5 mg SC daily 1
• Continue for hospitalization up to 8 days or until revascularization 1
• Contraindicated if creatinine clearance <30 mL/min 1
• Do NOT use as sole anticoagulant for primary PCI (Class III: Harm)—must add UFH bolus at time of PCI 1

Fibrinolytic Therapy Loading Doses

Indications:

• STEMI with symptom onset <12 hours when PCI will be delayed >120 minutes from first medical contact 1
• Fibrinolytics are NOT recommended in NSTE-ACS (Class III: Harm) 1

Common regimens (specific dosing varies by agent—consult institutional protocols):

• Tenecteplase, alteplase, or reteplase are standard options 1
• Must be accompanied by aspirin, clopidogrel (age-adjusted), and anticoagulation as detailed above 1

GP IIb/IIIa Inhibitors

Bail-out use only:

• Should be considered for bail-out if evidence of no-reflow or thrombotic complication during PCI 1
• Not recommended for routine upstream use before coronary anatomy is known (Class III) 1

Dosing if used:

• Abciximab: 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min) 1
• Eptifibatide: 180 mcg/kg IV bolus (double bolus 10 minutes apart), then 2 mcg/kg/min 1
• Tirofiban: 25 mcg/kg IV bolus, then 0.15 mcg/kg/min 1

Common Pitfalls to Avoid

• Do not delay aspirin administration—give immediately upon ACS recognition 2
• Do not use enteric-coated aspirin initially—absorption is too slow 1, 2, 3
• Do not give prasugrel before coronary anatomy is known in NSTE-ACS—wait until PCI 1, 2
• Do not give clopidogrel loading dose to patients >75 years receiving fibrinolytic therapy—start with 75 mg maintenance 1, 3
• Do not continue high-dose aspirin (>100 mg) with ticagrelor—reduces ticagrelor efficacy 1, 2
• Do not use fondaparinux as sole anticoagulant for primary PCI—must add UFH 1
• Do not mix UFH and enoxaparin within 12 hours—increases bleeding risk 1