What is the role of aspirin (acetylsalicylic acid) in primary cardiovascular (CV) prophylaxis in adults with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, or a family history of cardiovascular disease?

Aspirin for Primary Cardiovascular Prevention

Aspirin should NOT be routinely used for primary cardiovascular prevention in most adults, particularly those aged ≥60 years, as bleeding risks now equal or exceed cardiovascular benefits in contemporary populations with improved baseline risk management.

Current Evidence-Based Recommendations

Age-Based Approach

Adults ≥60 years:

• Aspirin is contraindicated for primary prevention regardless of cardiovascular risk level, as harms definitively outweigh benefits 1, 2
• The USPSTF 2022 guidance provides a Grade D recommendation (recommend against) for initiating aspirin in this age group 1, 2
• Age >70 years represents an absolute contraindication due to substantially increased bleeding risk (4-12 major bleeds per 1,000 over 5 years versus 2-4 in middle-aged adults) 3, 1

Adults aged 40-59 years:

• Consider aspirin 75-100 mg daily ONLY if ALL of the following criteria are met 1, 2:
  • 10-year ASCVD risk ≥10% 1, 2
  • No increased bleeding risk 1, 2
  • Patient willing to take daily aspirin after comprehensive shared decision-making 1, 2
• This represents a Grade C recommendation (selective use) from USPSTF, indicating marginal net benefit at best 1, 2

Special Population: Diabetes Mellitus

The evidence for aspirin in diabetic patients has fundamentally changed:

• The ASCEND trial (>15,000 diabetic patients) demonstrated that while aspirin reduced serious vascular events by 12%, major bleeding increased by 29% (from 3.2% to 4.1%) 3, 1
• For diabetic patients aged ≥50 years with ≥1 additional major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, CKD/albuminuria), aspirin 75-162 mg daily may be considered ONLY if bleeding risk is low 3, 1
• The American Diabetes Association emphasizes this should follow comprehensive shared decision-making, acknowledging that cardiovascular events prevented equal bleeding episodes induced 3, 1

Absolute Contraindications to Aspirin

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

• Age >70 years 1, 4
• History of gastrointestinal bleeding or peptic ulcer disease 1, 4
• Concurrent anticoagulation therapy 1, 5
• Thrombocytopenia or coagulopathy 1
• Chronic kidney disease 1
• Uncontrolled hypertension 1, 4
• Concurrent NSAID or corticosteroid use 1, 5
• Active bleeding or bleeding disorders 5
• Known aspirin allergy 3, 5

Risk-Benefit Analysis

The contemporary evidence demonstrates marginal or negative net benefit:

• For every 1,000 patients at moderate cardiovascular risk treated for 10 years: 19 fewer myocardial infarctions but 16 more major bleeding events 5
• In patients with ASCVD risk >1% per year, the number of cardiovascular events prevented equals the number of bleeding episodes induced 3, 1
• Aspirin has minimal to no impact on total mortality in primary prevention, with confidence intervals including zero benefit 5
• The number needed to treat to cause one major bleeding event (210) is lower than the number needed to prevent one cardiovascular event (265) 4

Dosing When Aspirin Is Prescribed

If aspirin is deemed appropriate after careful risk assessment:

• Use 75-100 mg daily (81 mg is standard US formulation) 3, 1, 5
• Doses of 75-162 mg are acceptable, but use the lowest effective dose to minimize bleeding 3, 5
• Doses >162 mg provide no additional cardiovascular benefit but significantly increase bleeding risk 5

Alternative for Aspirin Allergy

For documented aspirin allergy in patients requiring antiplatelet therapy:

• Clopidogrel 75 mg daily may be substituted 3, 4

Clinical Decision Algorithm

Follow this stepwise approach:

1. Determine if secondary prevention indication exists (history of MI, stroke, or established ASCVD) - if yes, aspirin 75-100 mg daily is strongly indicated and this is NOT primary prevention 1, 5

2. Screen for absolute contraindications - if ANY present, do not prescribe aspirin 1, 5, 4

3. Assess age:

   • If ≥60 years: Do not prescribe aspirin for primary prevention 1, 2
   • If 40-59 years: Proceed to step 4 1, 2

4. Calculate 10-year ASCVD risk:

   • If <10%: Do not prescribe aspirin 1, 2
   • If ≥10%: Proceed to step 5 1, 2

5. Assess bleeding risk factors (age >70, GI history, anticoagulation, CKD, uncontrolled HTN, NSAID use) - if ANY present, do not prescribe aspirin 1, 5

6. Engage in shared decision-making discussing that bleeding risks approximately equal cardiovascular benefits 3, 1, 2

Special Consideration: Hypertension

For hypertensive patients:

• Blood pressure must be controlled (<150/90 mmHg) before considering aspirin 1, 4
• Aspirin should only be considered if age ≥50 years with controlled BP, target organ damage, and 10-year CVD risk >15% 1
• Uncontrolled hypertension is an absolute contraindication 1, 4

Superior Alternative Strategies

These interventions provide greater mortality benefit than aspirin:

• Statin therapy for elevated LDL-C (target <70 mg/dL for high risk) has demonstrated mortality benefit in primary prevention 4
• Blood pressure optimization with individualized targets 4
• Lifestyle modifications including smoking cessation, Mediterranean diet, and regular physical activity 4

Common Pitfalls to Avoid

• Do not prescribe aspirin based solely on calculated 10-year cardiovascular risk without assessing bleeding risk 4
• Do not use controlled hypertension alone as justification to start aspirin in the absence of documented atherosclerotic disease 4
• Do not confuse primary and secondary prevention indications - aspirin remains strongly indicated for secondary prevention 1, 4
• Do not assume diabetes automatically warrants aspirin - the ASCEND trial showed bleeding risks largely counterbalance benefits 3, 1

Why Recommendations Have Changed

Three major trials (ARRIVE, ASCEND, ASPREE) published since 2018 fundamentally altered the evidence base:

• These trials showed either no benefit or only modest benefit on combined ischemic endpoints without impact on hard cardiovascular events (MI or stroke) 6
• The progressive reduction in baseline MACE risk due to improved primary prevention (statin use, smoking cessation, BP control) has reduced aspirin's absolute benefit 7, 6
• This led the ACC/AHA to downgrade aspirin from Class IIa to Class IIb (may be considered) and USPSTF to recommend against use in adults ≥60 years 1, 2