Should aspirin (acetylsalicylic acid) be used as primary prevention for cardiovascular disease in adults?

Aspirin for Primary Prevention of Cardiovascular Disease

Aspirin should NOT be routinely used for primary prevention of cardiovascular disease in most adults, particularly those aged 60 years or older, as the bleeding risks outweigh any cardiovascular benefits. For select adults aged 40-59 years with ≥10% 10-year cardiovascular disease risk and low bleeding risk, aspirin may be considered only after individualized shared decision-making that explicitly weighs the small net benefit against bleeding harms. 1, 2, 3, 4

Age-Based Recommendations

Adults ≥60 Years

• Aspirin is NOT recommended for primary prevention in this age group (Grade D recommendation from USPSTF 2022). 4
• The American College of Cardiology and American Heart Association specifically recommend against routine aspirin use in adults over 70 years (Class III: Harm). 1, 3
• Bleeding risk substantially outweighs any potential cardiovascular benefit in older adults. 1, 5
• For patients already taking aspirin for primary prevention who are ≥70 years, discontinuation should be strongly considered. 3

Adults 40-59 Years

• Aspirin may be considered ONLY if ALL of the following criteria are met: 4, 6
  • 10-year cardiovascular disease risk ≥10% (calculated using validated risk assessment tools)
  • No increased bleeding risk
  • Patient willingness to take daily aspirin after understanding the limited net benefit
• This is a Grade C recommendation, indicating the net benefit is small. 4
• The number of cardiovascular events prevented equals the number of bleeding episodes induced when ASCVD risk is >1% per year. 2, 3

Adults <40 Years

• Insufficient evidence to recommend aspirin for primary prevention. 3
• Generally not indicated unless exceptional circumstances exist. 2

Absolute Contraindications to Aspirin Use

Do not prescribe aspirin if any of the following are present: 1, 2

• Age >70 years
• History of gastrointestinal bleeding or peptic ulcer disease
• Concurrent anticoagulation therapy
• Thrombocytopenia or coagulopathy
• Chronic kidney disease
• Uncontrolled hypertension (BP >150/90 mmHg)
• Concurrent NSAID or corticosteroid use
• Age <21 years (risk of Reye syndrome) 3

Special Populations

Patients with Diabetes

• Aspirin is NOT routinely recommended for primary prevention in diabetic patients. 1, 2
• May be considered in select diabetic patients ≥50 years with at least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, chronic kidney disease/albuminuria) AND low bleeding risk. 2, 3
• The ASCEND trial showed a 12% reduction in serious vascular events but major bleeding increased from 3.2% to 4.1% (29% relative increase). 2, 3
• The European Society of Cardiology recommends against aspirin for primary prevention in diabetic patients at moderate cardiovascular risk (Class III). 1

Patients with Hypertension

• Blood pressure must be controlled (<150/90 mmHg) before considering aspirin. 2, 3
• Aspirin should only be considered if age ≥50 years with controlled BP, target organ damage, diabetes, or 10-year CVD risk >15%. 2, 3
• Uncontrolled hypertension is an absolute contraindication. 2

Risk-Benefit Analysis

Cardiovascular Benefits

• For every 1,000 low-risk patients treated for 10 years: 6 fewer myocardial infarctions. 2
• For every 1,000 moderate-risk patients treated for 10 years: 19 fewer myocardial infarctions. 2
• For every 1,000 high-risk patients treated for 10 years: 31 fewer myocardial infarctions. 2
• Minimal impact on total mortality with confidence intervals including zero benefit. 2

Bleeding Harms

• For every 1,000 low-risk patients treated for 10 years: 4 major bleeding events. 2
• For every 1,000 moderate-risk patients treated for 10 years: 16 major bleeding events. 2
• For every 1,000 high-risk patients treated for 10 years: 22 major bleeding events. 2
• Major bleeding occurs in 2-4 per 1,000 middle-aged adults over 5 years (4-12 per 1,000 in older adults). 2
• Gastrointestinal bleeding risk may be as high as 5 per 1,000 per year in real-world settings. 3
• Hemorrhagic stroke increases by 0-2 per 1,000 persons over 5 years. 2
• The number needed to treat to cause one major bleeding event (210) is lower than the number needed to treat to prevent one cardiovascular event (265). 1

Dosing When Aspirin Is Prescribed

If aspirin is indicated, use the lowest effective dose: 2, 3

• 75-100 mg daily (81 mg is the standard low-dose tablet in the US)
• Doses of 75-162 mg daily are acceptable 7, 2
• The ADAPTABLE trial showed no significant differences in cardiovascular events or major bleeding between 81 mg versus 325 mg daily in patients with established cardiovascular disease. 3

Clinical Decision Algorithm

Step 1: Determine if secondary prevention is indicated 2, 3

• Does the patient have established ASCVD (history of myocardial infarction, stroke, peripheral arterial disease, coronary revascularization)?
• If YES → Aspirin 75-100 mg daily is strongly recommended (this is secondary prevention, not primary prevention)
• If NO → Proceed to Step 2

Step 2: Screen for absolute contraindications 1, 2, 3

• Age >70 years?
• History of GI bleeding or peptic ulcer disease?
• Concurrent anticoagulation?
• Thrombocytopenia, coagulopathy, or chronic kidney disease?
• Uncontrolled hypertension?
• Concurrent NSAID or steroid use?
• If ANY YES → Do NOT prescribe aspirin
• If ALL NO → Proceed to Step 3

Step 3: Assess age and cardiovascular risk 2, 3, 4

• Age ≥60 years? → Do NOT prescribe aspirin
• Age <40 years? → Do NOT prescribe aspirin (insufficient evidence)
• Age 40-59 years? → Proceed to Step 4

Step 4: Calculate 10-year cardiovascular disease risk 2, 4

• Use validated risk assessment tools (ATP III guidelines or equivalent)
• Is 10-year CVD risk ≥10%?
  • If NO → Do NOT prescribe aspirin
  • If YES → Proceed to Step 5

Step 5: Shared decision-making 2, 3, 4

• Discuss that the net benefit is small
• Explain that cardiovascular events prevented approximately equal bleeding episodes induced
• Assess patient willingness to take daily aspirin
• If patient accepts after understanding risks → Consider aspirin 75-100 mg daily
• If patient declines or uncertain → Do NOT prescribe aspirin

Common Pitfalls to Avoid

• Do not prescribe aspirin based solely on 10-year cardiovascular risk calculation without assessing bleeding risk. 1, 2
• Do not use controlled hypertension alone as justification to start aspirin in the absence of documented atherosclerotic disease. 1, 2
• Do not confuse primary and secondary prevention indications – aspirin remains strongly indicated for secondary prevention. 1, 3
• Do not continue aspirin in patients >70 years who were started on it for primary prevention – reassess and strongly consider discontinuation. 3
• Do not assume aspirin prevents cardiovascular mortality – the impact on total mortality is minimal. 2

Superior Alternative Strategies for Primary Prevention

Instead of aspirin, prioritize these evidence-based interventions: 1

• Statin therapy if LDL-C is elevated (target <70 mg/dL for high risk; <55 mg/dL for very high risk) – statins have demonstrated mortality benefit in primary prevention
• Blood pressure optimization with individualized target of systolic BP 130-139 mmHg in elderly >65 years, diastolic BP <80 mmHg but not <70 mmHg
• Lifestyle modifications including smoking cessation, Mediterranean diet, and regular physical activity

Evolution of Guidelines

The 2022 USPSTF guidance represents a significant departure from earlier recommendations. 2 The 2002 USPSTF strongly recommended aspirin for adults at increased coronary heart disease risk (Grade A recommendation), particularly those with 5-year risk ≥3%. 7 The 2009 ACC/AHA guidelines recommended aspirin for men with 10-year CHD risk ≥20%. 7 However, recent large trials (ASPREE, ARRIVE, ASCEND) demonstrated that bleeding harms outweigh cardiovascular benefits in most primary prevention populations, leading to the current restrictive recommendations. 1, 5, 4