Why is a daily 325 mg aspirin prescribed for adults with prior myocardial infarction, ischemic stroke, or peripheral arterial disease for secondary prevention?

Why People Take 325 mg of Aspirin Daily

For adults with prior myocardial infarction, ischemic stroke, or peripheral arterial disease, a daily aspirin dose of 325 mg falls within the guideline-recommended range of 75–325 mg for secondary prevention, though current evidence supports using the lower end of this range (75–100 mg daily) for long-term maintenance to minimize bleeding risk while maintaining cardiovascular protection. 1, 2

The Evidence-Based Dosing Strategy

Acute vs. Maintenance Dosing

The confusion around 325 mg stems from conflicting recommendations for acute loading versus long-term maintenance:

• Acute events (MI, stroke, TIA): A loading dose of 160–325 mg is appropriate within the first 24–48 hours to achieve rapid platelet inhibition. 2, 3
• Long-term maintenance: After the acute phase, guidelines recommend 75–100 mg daily as the optimal maintenance dose for secondary prevention. 2, 4, 5

Why Lower Doses Are Preferred for Maintenance

The American Heart Association and European Society of Cardiology both recommend 75–100 mg daily for long-term secondary prevention because this dose provides equivalent cardiovascular protection to higher doses while significantly reducing bleeding complications. 4, 5

• Meta-analyses of secondary prevention trials show that doses from 75 mg to >1500 mg daily provide similar benefits on myocardial infarction, stroke, and cardiovascular death. 3
• The maintenance dose of 75–100 mg provides equivalent efficacy to higher doses (up to 1500 mg) while minimizing gastrointestinal bleeding risk. 2
• Major bleeding risk increases with higher aspirin doses without proportional cardiovascular benefit. 2, 6

Specific Recommendations by Condition

Post-Myocardial Infarction

• Loading: 162–325 mg non-enteric-coated aspirin immediately during acute MI. 5
• Maintenance: 81 mg daily indefinitely (preferred over higher doses to minimize bleeding). 5
• This strategy reduces 5-week vascular mortality by 23% and non-fatal vascular events by 50%. 5

Post-Ischemic Stroke or TIA

• Loading: 160–325 mg within 24–48 hours after ruling out intracranial hemorrhage. 2
• Maintenance: 75–100 mg daily for lifelong secondary prevention. 2
• For minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), dual antiplatelet therapy (aspirin + clopidogrel) is recommended for exactly 21 days, then transition to single-agent therapy. 2

Peripheral Arterial Disease

• Recommended range: 75–325 mg daily, though the European Society of Cardiology specifies 75–160 mg as preferred. 1, 4
• Clopidogrel shows 23.8% greater benefit than aspirin specifically in PAD patients and may be preferred. 5, 7

Common Clinical Pitfall: Continuing 325 mg Long-Term

Many patients remain on 325 mg daily indefinitely because the loading dose is never reduced to the appropriate maintenance dose. This practice increases bleeding risk without additional cardiovascular benefit:

• Gastrointestinal bleeding risk increases approximately 1.4–1.5 fold with aspirin 75–325 mg daily. 5
• Elderly patients face substantially higher bleeding risk, with major bleeding events occurring at approximately 5 per 1,000 per year. 4
• The lowest effective dose (75–81 mg) should be used to reduce bleeding complications while maintaining cardiovascular efficacy. 4

When 325 mg May Be Appropriate

The only scenarios where continuing 325 mg daily might be justified:

1. Acute phase (first 24–48 hours) of MI, stroke, or TIA as a loading dose. 2, 3
2. Symptomatic PAD where the patient and physician explicitly choose the higher end of the 75–325 mg range, though 75–160 mg is preferred. 1, 4
3. Aspirin resistance or inadequate platelet suppression documented on testing, though switching to clopidogrel is typically preferred over dose escalation. 8

Practical Algorithm for Aspirin Dosing

For patients with established cardiovascular disease:

1. Confirm the indication: Prior MI, ischemic stroke/TIA, or symptomatic PAD. 1, 4
2. Assess bleeding risk: History of GI bleeding, age ≥75 years, concurrent anticoagulation, or NSAID use. 4, 6
3. Choose maintenance dose:
   • Low-moderate bleeding risk: 75–81 mg daily (preferred). 4, 5
   • High bleeding risk but established CVD: Consider clopidogrel 75 mg daily as alternative. 4, 7
4. Add gastroprotection: Proton pump inhibitor if history of GI bleeding or concurrent anticoagulation. 2

Bottom Line

If a patient is taking 325 mg aspirin daily for secondary prevention beyond the first 48 hours after an acute event, the dose should be reduced to 75–100 mg daily unless there is a specific documented reason to continue the higher dose. 2, 4, 5 The 325 mg dose is a historical artifact from early trials and acute-phase protocols, not an evidence-based choice for long-term maintenance therapy. 3, 9