What are the recommendations for aspirin (acetylsalicylic acid) use in a patient with high Atherosclerotic Cardiovascular Disease (ASCVD) risk for primary prevention of cardiovascular events?

Aspirin for Primary Prevention in High ASCVD Risk

Low-dose aspirin (75-100 mg daily) might be considered only for highly select adults aged 40-70 years at higher ASCVD risk who have no bleeding risk factors, but this is a weak recommendation (Class IIb) reflecting that aspirin's modest cardiovascular benefit is largely offset by comparable bleeding risk in the modern era of evidence-based statin and antihypertensive therapy. 1, 2

The Fundamental Shift Away from Aspirin

The 2019 ACC/AHA guidelines downgraded aspirin to Class IIb (weak recommendation) for primary prevention, abandoning the previous 10% 10-year ASCVD risk threshold that once guided therapy. 1, 2 This reflects a critical reality: recent large trials demonstrate that when patients receive contemporary evidence-based therapies (statins, antihypertensives), aspirin prevents approximately the same number of ASCVD events as it causes major bleeding episodes. 2, 3

The number of cardiovascular events prevented equals the number of bleeding episodes induced in patients with over 1% annual ASCVD risk. 2

Why Recent Evidence Changed Practice

• The ASCEND trial showed only a 12% reduction in cardiovascular events but a 29% increase in major bleeding. 2
• Meta-regression analysis of 12 trials with nearly 1 million patient-years found no relationship between baseline ASCVD risk and aspirin's treatment effect—meaning aspirin does not become more beneficial as risk increases, contrary to longstanding assumptions. 3
• Recent trials consistently show that estimated ASCVD risk exceeds actual observed risk during follow-up, making risk-based selection less reliable. 1

Absolute Contraindications: When NOT to Use Aspirin

Aspirin should NOT be used routinely in adults over 70 years of age (Class III: Harm recommendation). 1, 2 This age group has greater bleeding risk than cardiovascular benefit regardless of calculated ASCVD risk. 2

Aspirin should NOT be used in any adult at increased bleeding risk (Class III: Harm recommendation). 1, 2 Specific high-risk scenarios include:

• History of gastrointestinal bleeding or peptic ulcer disease 1, 2
• Thrombocytopenia or coagulopathy 1, 2
• Chronic kidney disease 1, 2
• Concurrent use of NSAIDs, steroids, direct oral anticoagulants, or warfarin 1, 2
• Age >70 years 1, 2

When Aspirin MIGHT Be Considered (Rare Scenarios)

For the narrow population of adults aged 40-70 years at higher ASCVD risk with NO bleeding risk factors, aspirin 75-100 mg daily might be considered through shared decision-making. 1, 2 However, this is a weak recommendation reflecting equipoise between benefits and harms.

Emerging Exception: Elevated Lipoprotein(a)

Recent evidence suggests aspirin may provide approximately 50% reduction in coronary heart disease events and ASCVD mortality specifically in individuals with Lp(a) >50 mg/dL without clinical ASCVD. 4 This represents a potential subgroup where aspirin's benefit-risk ratio may be more favorable, though definitive guidance awaits further study. 4

Where Aspirin IS Strongly Indicated: Secondary Prevention

Aspirin remains strongly recommended (75-162 mg daily) for secondary prevention in patients with established ASCVD, where benefits far exceed risks. 2, 5 This includes patients with:

• Prior acute coronary syndrome (>1 year post-event) 5
• Prior revascularization 5
• Documented coronary stenosis >50% 5
• History of myocardial infarction or ischemic stroke 2

The optimal dose for secondary prevention is 75-100 mg daily, as higher doses increase gastrointestinal bleeding without proportional cardiovascular benefit. 5

Critical Pitfalls to Avoid

• Do not use the 10% 10-year ASCVD risk threshold as an automatic indication for aspirin—this outdated approach has been removed from current guidelines. 1, 2
• Do not overlook bleeding risk factors when calculating net benefit—bleeding risk is less well correlated with ASCVD risk than previously assumed. 1
• Do not continue aspirin in patients over 70 years without documented ASCVD—the harm outweighs benefit in this age group. 2
• Do not assume higher ASCVD risk means greater aspirin benefit—meta-regression shows no relationship between baseline risk and treatment effect. 3

Special Population: Diabetes

Aspirin is not generally recommended for primary prevention in diabetic patients. 2 It may be considered only through shared decision-making for diabetic patients at high cardiovascular risk with low bleeding risk, but this remains controversial. 2