What is the recommended dose of antiplatelets, such as aspirin (acetylsalicylic acid) or clopidogrel, for patients with conditions like acute coronary syndrome or stroke?

Antiplatelet Dosing Recommendations

For acute coronary syndrome (ACS), aspirin should be dosed at 81 mg daily (range 75-100 mg) when used as part of dual antiplatelet therapy (DAPT), and for acute ischemic stroke or TIA, a loading dose of aspirin 160-325 mg should be given initially, followed by 75-100 mg daily for maintenance.

Acute Coronary Syndrome (ACS)

Aspirin Dosing

• Daily aspirin dose of 81 mg (range 75-100 mg) is recommended for all patients with ACS treated with DAPT, regardless of whether they receive medical therapy alone, fibrinolytic therapy, or PCI 1
• This low-dose regimen applies equally to NSTE-ACS and STEMI patients 1
• Higher aspirin doses (>100 mg daily) increase bleeding risk without improving efficacy 2

P2Y12 Inhibitor Dosing in ACS

For ACS with PCI:

• Clopidogrel: 300 mg loading dose, then 75 mg daily for at least 12 months 1, 3
• Prasugrel: 10 mg daily for at least 12 months (avoid if prior stroke/TIA) 1
• Ticagrelor: Preferred over clopidogrel; dose not specified in guidelines but standard is 180 mg loading, then 90 mg twice daily for at least 12 months 1

For ACS with medical therapy alone (no revascularization):

• Clopidogrel or ticagrelor should be continued for at least 12 months 1
• Ticagrelor is reasonable to use in preference to clopidogrel 1

For STEMI with fibrinolytic therapy:

• Clopidogrel should be continued for minimum 14 days, ideally at least 12 months 1
• Aspirin 81 mg daily (range 75-100 mg) 1

Important Caveats for ACS

• After CABG in ACS patients, resume P2Y12 inhibitor therapy to complete 12 months of DAPT 1
• Prasugrel is contraindicated in patients with prior stroke or TIA 1
• In high bleeding risk patients after DES, discontinuation of P2Y12 therapy after 6 months may be reasonable 1

Acute Ischemic Stroke and TIA

Loading Dose Strategy

• Aspirin 160-325 mg as a single loading dose should be administered within 24-48 hours after ruling out intracranial hemorrhage 4, 5
• For patients receiving IV alteplase, delay aspirin until 24 hours post-thrombolysis 4
• For patients unable to swallow, use rectal aspirin 325 mg daily or aspirin 81 mg daily via enteral tube 4, 5

Dual Antiplatelet Therapy for Minor Stroke/High-Risk TIA

Loading doses:

• Aspirin 160-325 mg PLUS clopidogrel 300-600 mg within 12-24 hours of symptom onset 4, 6, 5
• Alternative: Aspirin 300-325 mg PLUS ticagrelor 180 mg 4, 5

Maintenance regimen:

• Aspirin 81 mg daily PLUS clopidogrel 75 mg daily for exactly 21 days, then switch to single antiplatelet therapy 4, 6
• Alternative: Aspirin 75-100 mg daily PLUS ticagrelor 90 mg twice daily for 30 days 4, 5

Long-Term Secondary Prevention (After 21-30 Days)

• Aspirin 75-100 mg daily as first-line single antiplatelet therapy 4
• Clopidogrel 75 mg daily as equally effective alternative 4
• Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily is a reasonable alternative 4
• Do NOT continue aspirin plus clopidogrel beyond 21-30 days due to significantly increased hemorrhage risk without additional benefit 4

Stable Coronary Artery Disease and Peripheral Arterial Disease

Chronic Prevention

• Aspirin 75-162 mg daily for patients with established coronary artery disease 1
• Clopidogrel 75 mg daily is an alternative for aspirin-intolerant patients 1
• For symptomatic peripheral artery disease: aspirin 75-325 mg daily OR clopidogrel 75 mg daily 1

Post-CABG

• Aspirin 100-325 mg daily should be started within 6 hours after surgery and continued for 1 year 1
• Clopidogrel 75 mg daily is a reasonable alternative if aspirin-intolerant 1

Critical Dosing Principles Across All Conditions

Why Low-Dose Aspirin is Preferred

• Bleeding risk increases with aspirin dose in both monotherapy and DAPT, without improved efficacy 2
• In the CURE trial, major bleeding increased from 1.9% (≤100 mg) to 3.7% (≥200 mg) with placebo, and from 3.0% to 4.9% with clopidogrel 2
• The optimal daily aspirin dose is 75-100 mg when combined with clopidogrel 2

Pharmacological Rationale for Loading Doses

• Standard clopidogrel 75 mg daily requires approximately 5 days to achieve maximal platelet inhibition 4, 6
• Loading doses (300-600 mg clopidogrel, 160-325 mg aspirin) provide rapid platelet inhibition within hours 4, 6, 3
• This is critical in acute thrombotic events where immediate antiplatelet effect is needed 4, 6

Common Pitfalls to Avoid

• Never use higher aspirin doses (>100 mg daily) for maintenance therapy after the loading phase, as this increases bleeding without improving outcomes 1, 2
• Never continue DAPT beyond 21-30 days in stroke patients unless specific high-risk features warrant it, as bleeding risk outweighs benefit 4
• Never use aspirin as substitute for thrombolysis or mechanical thrombectomy in eligible acute stroke patients 4
• Avoid enteric-coated aspirin for loading doses due to slower onset of action 4