What are the indications for aspirin (acetylsalicylic acid) for primary prevention of cardiovascular events?

Indications for Aspirin in Primary Prevention

Aspirin for primary prevention should be reserved for select high-risk patients after careful consideration of bleeding risk, and is generally NOT recommended for routine use in most adults without established cardiovascular disease.

Current Evidence-Based Approach

The landscape of aspirin for primary prevention has shifted dramatically based on recent high-quality trials. The most favorable risk-benefit ratio exists only in carefully selected populations.

Who Should Consider Aspirin for Primary Prevention

Adults with diabetes aged ≥50 years who meet ALL of the following criteria 1, 2:

• At least one additional major cardiovascular risk factor (hypertension, dyslipidemia, smoking, family history of premature ASCVD, or chronic kidney disease/albuminuria)
• 10-year ASCVD risk ≥10%
• Low bleeding risk (no history of GI bleeding, no concurrent anticoagulation, controlled blood pressure)
• Dose: 75-162 mg daily 1, 2

Important caveat: The ASCEND trial (2018) showed that in diabetic patients, aspirin reduced cardiovascular events by only 12% but increased major bleeding by 29%, meaning the number of events prevented roughly equals the number of bleeding episodes induced 1. This makes the decision highly preference-sensitive.

Adults aged 40-59 years with ≥10% 10-year ASCVD risk 3:

• This receives only a Class IIb recommendation ("may be considered") from ACC/AHA
• Net benefit is small even in this population
• Must have no increased bleeding risk

Who Should NOT Receive Aspirin for Primary Prevention

Absolute contraindications 2, 3:

• Adults aged >70 years (ASPREE trial showed increased mortality and no benefit) 1, 4
• Adults aged <50 years with diabetes and no other major risk factors 1
• 10-year ASCVD risk <10% 3
• History of gastrointestinal bleeding or peptic ulcer disease 2, 3
• Uncontrolled hypertension 2, 3
• Concurrent use of anticoagulants (warfarin, DOACs), NSAIDs, or corticosteroids 2, 3
• Thrombocytopenia or coagulopathy 3
• Chronic kidney disease 3
• Age <21 years (risk of Reye syndrome) 1

Quantifying the Risk-Benefit Balance

Bleeding risks are substantial 1, 2:

• Major gastrointestinal bleeding: 2-4 per 1,000 middle-aged adults over 5 years (4-12 per 1,000 in older adults)
• Hemorrhagic stroke: 0-2 per 1,000 persons over 5 years
• Relative risk of major GI bleeding increases by 48-49% even with low doses 5, 4

Cardiovascular benefits in primary prevention are modest 5, 6:

• Recent meta-analyses show aspirin reduces nonfatal MI by 21% in healthy individuals with risk factors
• No effect on cardiovascular death in primary prevention populations
• In diabetic patients specifically, aspirin showed NO effect on nonfatal MI or cardiovascular death 5

The Paradigm Shift: Why Guidelines Changed

Three landmark 2018 trials (ARRIVE, ASCEND, ASPREE) fundamentally altered recommendations 6, 4:

• ASPREE (elderly population): No benefit on disability-free survival, increased major hemorrhage and unexpectedly increased all-cause mortality
• ASCEND (diabetes): Small benefit offset by comparable bleeding risk
• ARRIVE (high-risk middle-aged adults): No effect on major cardiovascular events, increased GI bleeding

These trials demonstrated that in modern populations with better control of other risk factors (hypertension, cholesterol), aspirin's incremental benefit has diminished while bleeding risks remain constant.

Optimal Dosing When Indicated

75-100 mg daily is the recommended dose 2, 3:

• In the U.S., the most common formulation is 81 mg 1
• Higher doses (up to 162 mg) are acceptable but offer no additional benefit and may increase bleeding risk 1

Critical Clinical Pitfalls to Avoid

Do not prescribe aspirin based solely on age or single risk factor 3:

• Requires formal ASCVD risk calculation (use validated tools like the ACC/AHA Pooling Cohort Equation)
• The 5-year cardiovascular risk threshold where benefits exceed harms is ≥3% 1

Do not ignore the bleeding risk assessment 2, 3:

• Always specifically ask about history of GI bleeding, peptic ulcer disease
• Check for concurrent medications that increase bleeding risk
• Verify blood pressure is controlled (<150/90 mmHg in hypertensive patients) 2

Do not confuse primary and secondary prevention 1, 2:

• For patients with established ASCVD (prior MI, stroke, revascularization), aspirin is STRONGLY recommended and benefits far outweigh risks
• This is an entirely different risk-benefit calculation than primary prevention

Special Population: Hypertension

For hypertensive patients aged ≥50 years 2, 3:

• Consider aspirin 75-81 mg daily only if blood pressure is controlled (<150/90 mmHg) AND patient has target organ damage, diabetes, or 10-year CVD risk >15%
• The HOT trial showed 15% reduction in cardiovascular events and 36% reduction in MI, but major bleeds doubled 2

The Bottom Line Algorithm

1. Is this secondary prevention? (prior MI, stroke, revascularization) → YES: Prescribe aspirin 75-100 mg daily 2, 3

2. Is patient >70 years old? → YES: Do NOT prescribe for primary prevention 1, 3

3. Calculate 10-year ASCVD risk → If <10%: Do NOT prescribe 3

4. Assess bleeding risk factors → If ANY present: Do NOT prescribe 2, 3

5. If 10-year risk ≥10% AND no bleeding risk → Consider aspirin 75-100 mg daily with shared decision-making, emphasizing that benefits are small and bleeding risk is real 1, 2, 3

The evidence strongly suggests that for most adults without established cardiovascular disease, the risk of daily aspirin outweighs the benefit 6, 4. The era of routine aspirin for primary prevention has ended.