What is the recommended dose of aspirin (acetylsalicylic acid) for primary prevention of cardiovascular events?

Aspirin for Primary Prevention of Cardiovascular Disease

For primary prevention, low-dose aspirin 75-100 mg daily may be considered in adults aged 40-59 years with ≥10% 10-year ASCVD risk and no increased bleeding risk, but the net benefit is small and aspirin should NOT be used in adults over age 70 or those with any bleeding risk factors. 1

Patient Selection Algorithm

Step 1: Exclude Absolute Contraindications

Do NOT prescribe aspirin if ANY of the following are present:

• Age >70 years (harm exceeds benefit) 1, 2
• History of gastrointestinal bleeding or peptic ulcer disease 1, 2
• Concurrent anticoagulation (warfarin, DOACs) 1, 2
• Thrombocytopenia or coagulopathy 1, 2
• Chronic kidney disease 1, 2
• Concurrent NSAID or steroid use 1, 2
• Uncontrolled hypertension 1, 2

Step 2: Calculate 10-Year ASCVD Risk

• If <10% risk: Do NOT prescribe aspirin—bleeding risks outweigh minimal cardiovascular benefits 1, 2
• If ≥10% risk AND age 40-59 years: Proceed to Step 3 1
• If ≥10% risk AND age 60-70 years: Exercise extreme caution; benefits are marginal 3, 1

Step 3: Special Population Considerations

For patients with diabetes:

• Age ≥50 years with at least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or albuminuria) may be considered for aspirin 75-162 mg daily 1, 4, 2
• The ASCEND trial showed only 12% reduction in serious vascular events but major bleeding increased by 29% (from 3.2% to 4.1%) 2

For patients with hypertension:

• Only consider aspirin if age ≥50 years with controlled blood pressure (<150/90 mmHg), target organ damage or diabetes, AND 10-year CVD risk >15% 1, 4
• Blood pressure MUST be controlled before initiating aspirin 4

Recommended Dosing When Aspirin Is Prescribed

The optimal dose is 75-100 mg daily (81 mg tablet in the US). 3, 1, 2

• Acceptable dose range: 75-162 mg daily 1, 4
• Use the lowest effective dose to minimize bleeding risk while maintaining efficacy 1, 2
• The ADAPTABLE trial confirmed no difference in cardiovascular events or bleeding between 81 mg and 325 mg daily doses 4

Quantifying the Risk-Benefit Balance

Bleeding risks:

• Major gastrointestinal bleeding occurs in 2-4 per 1,000 middle-aged adults over 5 years (4-12 per 1,000 in older adults) 3, 1, 4, 2
• Hemorrhagic stroke increases by 0-2 per 1,000 persons over 5 years 3, 1, 4, 2
• Relative risk of major GI bleeding is 1.6 even with low doses 4, 2

Cardiovascular benefits:

• In patients with ≥10% 10-year ASCVD risk, aspirin reduces myocardial infarction by approximately 28% 3
• The number of cardiovascular events prevented equals the number of bleeding episodes induced when ASCVD risk is >1% per year 1, 2
• Aspirin slightly reduces total mortality regardless of cardiovascular risk profile if taken over 10 years 3

Critical Clinical Pitfalls to Avoid

Do not prescribe aspirin for low-risk individuals: Those with <10% 10-year ASCVD risk derive minimal benefit that is outweighed by bleeding risk 1, 2

Do not ignore age as a contraindication: Age >70 years is an absolute contraindication for primary prevention—the balance shifts to greater risk than benefit 1, 2

Do not prescribe aspirin with uncontrolled hypertension: Blood pressure must be controlled (<150/90 mmHg) before initiating aspirin to avoid hemorrhagic complications 1, 4, 2

Do not overlook concurrent medications: NSAIDs, steroids, and anticoagulants are absolute contraindications due to compounded bleeding risk 1, 2

Strength of Recommendation

The American College of Chest Physicians gives aspirin for primary prevention a Grade 2B recommendation (weak recommendation, moderate-quality evidence) for persons aged ≥50 years 3. The 2019 ACC/AHA guideline downgraded this to a Class IIb recommendation (may be considered) for adults aged 40-70 years at higher ASCVD risk but without increased bleeding risk 1, 2. This reflects the narrow margin between benefit and harm, with the reduction in myocardial infarction being closely balanced with an increase in major bleeds 3.

Shared Decision-Making Framework

Engage patients in discussion about:

• Their calculated 10-year ASCVD risk using validated risk calculators 4
• Individual bleeding risk factors (age, GI history, concurrent medications) 1, 4
• Patient values: those who value preventing MI substantially higher than avoiding GI bleeding are more likely to choose aspirin 3
• Understanding that benefits are most clearly established for secondary prevention, not primary prevention 4