What is the appropriate dose of aspirin (acetylsalicylic acid) for primary and secondary prevention of cardiovascular disease?

Aspirin Dosing for Cardiovascular Disease Prevention

For cardiovascular disease prevention, the recommended dose of aspirin is 75-100 mg daily for secondary prevention, while for primary prevention, aspirin at 75-162 mg daily should only be considered in select adults aged 40-59 years with ≥10% 10-year ASCVD risk and low bleeding risk. 1

Secondary Prevention Recommendations

Aspirin therapy is clearly beneficial for secondary prevention in patients with established cardiovascular disease:

• Dose: 75-162 mg daily 2, 1
• Patient population: All patients with established atherosclerotic cardiovascular disease (history of myocardial infarction, stroke, peripheral arterial disease) 2
• Alternative: For patients with documented aspirin allergy, clopidogrel 75 mg daily should be used 2
• Special consideration: Dual antiplatelet therapy (low-dose aspirin plus P2Y12 inhibitor) is reasonable for one year after acute coronary syndrome 2

The benefits of aspirin in secondary prevention are substantial, with approximately 25% reduction in serious vascular events 3. In this high-risk population, the benefits clearly outweigh the bleeding risks.

Primary Prevention Recommendations

The role of aspirin in primary prevention is more nuanced and has evolved significantly in recent years:

Age-Based Recommendations:

• Ages 40-59 years: Consider aspirin 75-162 mg daily only if 10-year ASCVD risk ≥10% and low bleeding risk 1, 4
• Ages ≥60 years: Aspirin is NOT recommended regardless of cardiovascular risk 1, 4
• Ages <40 years: Insufficient evidence to recommend aspirin 1
• Ages <21 years: Aspirin is contraindicated due to risk of Reye syndrome 2

Risk-Based Algorithm:

1. Calculate 10-year ASCVD risk using a validated calculator

2. Assess bleeding risk factors:

   • Age >70 years
   • History of GI bleeding/ulcers
   • Concurrent anticoagulant or NSAID use
   • Uncontrolled hypertension
   • Renal disease
   • Anemia
   • Thrombocytopenia
   • Coagulopathy
   • Chronic kidney disease 1

3. Apply recommendations based on risk profile:

   • High CV risk (≥10%) + Low bleeding risk = Consider aspirin 75-162 mg daily
   • Moderate CV risk (6-10%) + Low bleeding risk = Individualized decision
   • Low CV risk (<6%) or High bleeding risk = Aspirin NOT recommended 1

Special Considerations for Diabetes

For patients with diabetes:

• Aspirin 75-162 mg daily may be considered for primary prevention in those aged ≥50 years with at least one additional major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or albuminuria) 2
• Not recommended for low-risk patients with diabetes (younger patients without additional risk factors) 2

Optimal Dosing

The evidence supports using the lowest effective dose to minimize bleeding risk:

• Secondary prevention: 75-100 mg daily is as effective as higher doses 1, 5
• Primary prevention: 75-162 mg daily if indicated 2, 1
• Acute MI: Initial loading dose of 160-325 mg, followed by 75-150 mg daily 1

The most common low-dose tablet in the US is 81 mg 2. There is little evidence to support any specific dose within the recommended range, but using the lowest possible dose helps reduce side effects 2.

Potential Harms and Monitoring

• Major bleeding risk increases by 29-48% with aspirin therapy 1
• GI bleeding occurs in 2-4 per 1,000 middle-aged individuals and 4-12 per 1,000 older individuals over 5 years 1
• Hemorrhagic stroke risk increases by 0-2 per 1,000 persons over 5 years 1

Key Pitfalls to Avoid

1. Overuse in primary prevention: Recent evidence has shifted recommendations away from routine aspirin use for primary prevention, especially in adults ≥60 years 4
2. Inappropriate dosing: Higher doses (>325 mg) do not provide additional cardiovascular benefit but increase bleeding risk 5
3. Failure to consider bleeding risk: Always assess bleeding risk before recommending aspirin 1
4. Neglecting other cardiovascular risk reduction strategies: Aspirin should be an adjunct, not an alternative, to managing other cardiovascular risk factors 3
5. Discontinuing aspirin in secondary prevention: The benefits of aspirin in secondary prevention clearly outweigh the risks, and therapy should be lifelong unless contraindicated 2, 1

In summary, aspirin dosing should be carefully tailored based on the prevention context (primary vs. secondary), age, cardiovascular risk, and bleeding risk factors, with 75-100 mg daily being the optimal dose for most indications.