What is the role of low-dose aspirin (acetylsalicylic acid) in primary prevention of atherosclerotic cardiovascular disease (ASCVD)?

Low-Dose Aspirin for Primary Prevention of ASCVD

Low-dose aspirin is generally not recommended for routine primary prevention of atherosclerotic cardiovascular disease (ASCVD) due to the increased bleeding risk that often outweighs cardiovascular benefits. 1, 2

Current Recommendations by Age Group

• Adults >70 years: Aspirin should NOT be administered for primary prevention of ASCVD regardless of risk factors, as bleeding risks clearly outweigh cardiovascular benefits 1, 2
• Adults 40-70 years: Aspirin (75-100 mg daily) might be considered ONLY for select individuals at higher ASCVD risk without increased bleeding risk 1, 2
• Adults <40 years: Insufficient evidence to recommend aspirin for primary prevention 2
• Adults <21 years: Aspirin is contraindicated due to risk of Reye syndrome 1

Risk-Benefit Assessment

Benefits

• Modest reduction in ischemic vascular events (approximately 12% relative risk reduction) 2, 3
• The absolute decrease in events depends on underlying ASCVD risk 1, 2

Risks

• Increased risk of gastrointestinal bleeding (up to 5 per 1,000 per year in real-world settings) 1
• Major bleeding risk increased by approximately 40% with aspirin use 2, 4
• In the ASPREE trial, the rate of major hemorrhage was 8.6 events vs. 6.2 events per 1,000 person-years (HR 1.38; 95% CI 1.18-1.62; P < 0.001) 1

Net Benefit Analysis

• For adults with ASCVD risk >1% per year, the number of ASCVD events prevented will be similar to the number of bleeding episodes induced 1, 2
• However, recent meta-regression analysis found that aspirin's treatment effect does not increase as ASCVD risk increases, challenging the hypothesis that higher-risk primary prevention patients benefit more 3

Decision-Making Algorithm for Aspirin in Primary Prevention

1. First, determine if secondary prevention is indicated:

   • If patient has established ASCVD (prior MI, stroke, or documented atherosclerotic disease) → Aspirin IS recommended (75-162 mg/day) 1, 5

2. If for primary prevention, check patient age:

   • If >70 years → Do NOT use aspirin 1, 2
   • If <40 years → Insufficient evidence to recommend aspirin 2

3. For patients 40-70 years, assess:

   • ASCVD risk factors: Family history of premature ASCVD, hypertension, dyslipidemia, smoking, diabetes, chronic kidney disease/albuminuria 1
   • Bleeding risk factors: History of GI bleeding, peptic ulcer disease, thrombocytopenia, coagulopathy, CKD, concurrent use of medications that increase bleeding risk (NSAIDs, steroids, anticoagulants) 1, 2

4. Consider aspirin ONLY if:

   • High ASCVD risk (typically >10% 10-year risk) 1, 2
   • AND low bleeding risk 1, 2
   • AND patient is willing to take daily medication long-term 2

Special Considerations

Role of Coronary Artery Calcium (CAC) Score

• CAC scoring may help identify individuals who would benefit from aspirin despite not meeting traditional risk thresholds 6, 4
• Patients with CAC ≥100 may derive net benefit from aspirin if bleeding risk is low 6, 4
• Patients with CAC = 0 have very high NNT (number needed to treat) and should generally avoid aspirin for primary prevention 4

Patients with Diabetes

• Aspirin (75-162 mg/day) may be considered for adults with diabetes who are at increased ASCVD risk, after comprehensive discussion of benefits versus bleeding risks 1
• This includes both men and women aged ≥50 years with diabetes and at least one additional major risk factor who are not at increased risk of bleeding 1

Dosing Considerations

• When indicated, low-dose aspirin (75-100 mg daily) is preferred over higher doses to minimize bleeding risk 5, 2
• In the US, the most common low-dose tablet is 81 mg 2

For Patients Already on Aspirin for Primary Prevention

• If >70 years or at increased bleeding risk: Discontinuation should be strongly considered 2
• If 40-70 years: Reassess risk-benefit profile based on current guidelines 2

Common Pitfalls and Caveats

• Overestimating the benefit of aspirin in primary prevention based on older studies that didn't account for modern preventive therapies 1, 3
• Failing to reassess bleeding risk in patients on long-term aspirin therapy 1, 2
• Assuming that higher ASCVD risk automatically means greater benefit from aspirin - recent evidence contradicts this assumption 3
• Not considering that bleeding and cardiovascular complications have different impacts on quality of life and mortality 1