What are the recommended antiplatelet loading doses for an adult presenting with acute coronary syndrome (unstable angina, NSTEMI, or STEMI), including aspirin and P2Y12 inhibitors and considerations for contraindications or inability to take oral medication?

Antiplatelet Loading Doses in Acute Coronary Syndrome

All patients with ACS should receive an immediate loading dose of 162-325 mg of non-enteric coated, chewable aspirin as soon as possible after presentation, followed by a P2Y12 inhibitor loading dose based on the specific clinical scenario and planned management strategy. 1

Aspirin Loading and Maintenance

• Administer 162-325 mg of non-enteric coated aspirin immediately upon ACS presentation, regardless of whether the patient is already on aspirin therapy 1
• The aspirin should be chewed when possible to achieve rapid onset of antiplatelet action 1, 2
• Avoid enteric-coated formulations initially due to delayed and reduced absorption 1
• Maintenance dose is 75-100 mg daily (not 81-325 mg as previously recommended), as this lower dose reduces bleeding risk without compromising efficacy 1

Alternative Routes When Oral Administration Not Possible

• Rectal administration (325 mg/day) is a reasonable alternative when patients cannot take oral medication 2
• Intravenous aspirin may be used where available 1

P2Y12 Inhibitor Selection and Loading Doses

For NSTE-ACS (Unstable Angina/NSTEMI)

Early Invasive Strategy (angiography planned within 24 hours):

• Clopidogrel: 300-600 mg loading dose (600 mg preferred for faster onset), then 75 mg daily 1
• Ticagrelor: 180 mg loading dose, then 90 mg twice daily - preferred over clopidogrel 1
• Prasugrel: 60 mg loading dose at time of PCI (after coronary anatomy defined), then 10 mg daily if body weight ≥60 kg and age <75 years 1, 3

Delayed Invasive or Ischemia-Guided Strategy (angiography >24 hours or conservative management):

• Administer clopidogrel or ticagrelor upstream (before angiography) with loading doses as above 1
• This approach reduces MACE when angiography timing is anticipated to be >24 hours 1

For STEMI

Primary PCI Strategy:

• Prasugrel 60 mg or ticagrelor 180 mg should be administered to reduce MACE and stent thrombosis 1
• Clopidogrel 300-600 mg is recommended when prasugrel or ticagrelor are unavailable, contraindicated, or not tolerated 1

Fibrinolytic Therapy:

• Clopidogrel 300 mg loading dose if age ≤75 years 1
• Clopidogrel 75 mg (no loading dose) if age >75 years 1
• Clopidogrel should be administered concurrently with fibrinolytic therapy 1

Critical Dosing Considerations

Prasugrel-Specific Restrictions

• Contraindicated in patients with prior stroke or TIA 3
• Reduce maintenance dose to 5 mg daily if body weight <60 kg 1, 3
• Use with caution (5 mg maintenance) if age ≥75 years, only in high-risk patients (diabetes or prior MI) 3
• Only administer after coronary anatomy is defined at time of PCI 1

Ticagrelor-Specific Considerations

• Aspirin maintenance dose must be ≤100 mg daily when used with ticagrelor (specifically 81 mg recommended) 1
• Higher aspirin doses reduce ticagrelor efficacy 1

Clopidogrel Limitations

• Less effective in CYP2C19 poor metabolizers - consider alternative P2Y12 inhibitor in these patients 4
• Avoid concomitant omeprazole or esomeprazole as they significantly reduce clopidogrel's antiplatelet activity 4

Aspirin Allergy or Intolerance

• Administer P2Y12 inhibitor alone (clopidogrel, prasugrel, or ticagrelor) with loading dose followed by maintenance dosing 1
• This is a Class I recommendation when aspirin cannot be used due to hypersensitivity or major gastrointestinal intolerance 1

Common Pitfalls to Avoid

• Do NOT use high-dose aspirin maintenance (≥160 mg) - associated with increased bleeding without improved outcomes 1
• Do NOT delay aspirin administration - it should be given immediately upon ACS recognition 1
• Do NOT give prasugrel before knowing coronary anatomy in NSTE-ACS patients 1
• Do NOT continue high-dose aspirin with ticagrelor - must reduce to ≤100 mg daily 1
• Do NOT use enteric-coated aspirin initially - absorption is too slow for acute setting 1