What are the guidelines for aspirin (acetylsalicylic acid) use in primary prevention of cardiovascular events?

Aspirin Guidelines for Cardiovascular Prevention

Primary Prevention: Highly Selective Use Only

For adults aged 40-59 years with ≥10% 10-year ASCVD risk and no bleeding risk factors, aspirin 75-100 mg daily may be considered, but the net benefit is small and the 2019 ACC/AHA guideline gives this only a Class IIb recommendation (may be considered). 1, 2

Who Should NOT Receive Aspirin for Primary Prevention

• Age >70 years is an absolute contraindication - harm exceeds benefit 1, 3, 2
• History of gastrointestinal bleeding or peptic ulcer disease 1, 3
• Concurrent anticoagulation (warfarin, DOACs) 1, 3
• Thrombocytopenia or coagulopathy 1, 3
• Chronic kidney disease 1, 3
• Uncontrolled hypertension 1, 4, 3
• Concurrent NSAID or steroid use 1, 3
• 10-year ASCVD risk <10% - minimal benefit outweighed by bleeding risk 1, 3

Special Populations for Primary Prevention

Diabetic patients aged ≥50 years: Aspirin 75-162 mg daily may be considered only if they have at least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or albuminuria) AND no increased bleeding risk 4, 3

• The ASCEND trial showed only 12% reduction in serious vascular events, but major bleeding increased from 3.2% to 4.1% (29% relative increase) 3
• Recent meta-analyses found no statistically significant reduction in major cardiovascular events or all-cause mortality in diabetic patients without pre-existing CVD 4

Hypertensive patients aged ≥50 years: Consider aspirin 75-81 mg daily only if blood pressure is controlled (<150/90 mmHg) AND they have target organ damage, diabetes, or 10-year CVD risk >15% 1, 4

• The HOT trial demonstrated 15% reduction in major cardiovascular events and 36% reduction in MI, but non-fatal major bleeds were twice as common 4

Secondary Prevention: Strong Indication

For patients with established cardiovascular disease (previous MI, coronary revascularization, or significant obstructive CAD on imaging), aspirin 75-100 mg daily is strongly recommended as lifelong therapy after completion of dual antiplatelet therapy. 1, 4

• Benefits far outweigh bleeding risks in secondary prevention 1, 4
• For diabetic patients with established ASCVD, aspirin 75-162 mg daily is strongly recommended 1, 4
• Following coronary stenting, combine aspirin 75-100 mg daily with clopidogrel for up to 6-12 months, then transition to aspirin monotherapy 1, 4

Optimal Dosing

The recommended dose for both primary and secondary prevention is 75-100 mg daily (81 mg is the most common formulation in the US). 1, 4, 3

• Doses of 75-162 mg daily are acceptable 5, 1, 3
• The ADAPTABLE trial showed no difference in cardiovascular events or bleeding between 81 mg and 325 mg daily doses 4
• Lower doses (75-81 mg) provide equivalent cardiovascular protection while significantly reducing bleeding complications 4, 6
• For acute MI or acute stroke, use a loading dose of 162.5-325 mg, then transition to 75-100 mg daily 6

Bleeding Risk Quantification

• Major gastrointestinal bleeding occurs in 2-4 per 1,000 middle-aged adults over 5 years (4-12 per 1,000 in older adults) 5, 1, 3
• Hemorrhagic stroke increases by 0-2 per 1,000 persons over 5 years 5, 1, 3
• Relative risk of major GI bleeding is 1.6 even with low doses 1, 4
• In patients with ASCVD risk >1% per year, the number of cardiovascular events prevented equals the number of bleeding episodes induced 3

Clinical Decision Algorithm

1. Determine if secondary prevention indication exists: Previous MI, stroke, coronary revascularization, or significant obstructive CAD → Prescribe aspirin 75-100 mg daily 1, 4

2. For primary prevention candidates (age 40-59, ≥10% 10-year ASCVD risk):

   • Screen for absolute contraindications (age >70, GI bleeding history, concurrent anticoagulation, uncontrolled hypertension) 1, 3
   • If contraindications present → Do not prescribe aspirin 1, 3
   • If no contraindications → Consider aspirin 75-100 mg daily, but emphasize small net benefit 1, 2

3. For age ≥60 years without established CVD: Do not initiate aspirin - no net benefit 2

Alternative Antiplatelet Therapy

• For documented aspirin allergy requiring antiplatelet therapy, substitute clopidogrel 75 mg daily 1, 4, 3

Common Pitfalls to Avoid

• Do not prescribe aspirin for low-risk individuals (<10% 10-year ASCVD risk) - minimal benefit outweighed by bleeding risk 1, 3
• Do not ignore bleeding risk factors - always assess for GI bleeding history, concurrent anticoagulation, and uncontrolled hypertension before prescribing 1, 4
• Do not continue dual antiplatelet therapy indefinitely post-PCI - transition to aspirin monotherapy after 6-12 months unless specific indications exist 1, 4
• Do not use higher doses (>100 mg) for long-term therapy - no additional benefit and increased bleeding risk 1, 4, 6
• Recognize sex differences in primary prevention: Aspirin reduces MI in men but not women, while reducing stroke in women but not men 5, 4