Aspirin for Primary Prevention of Cardiovascular Disease
Aspirin should NOT be routinely used for primary prevention of atherosclerotic cardiovascular disease in most adults, as recent high-quality evidence demonstrates that bleeding risks equal or exceed cardiovascular benefits in the modern era of optimized statin and blood pressure therapy. 1, 2
Current Guideline Recommendations
The 2019 ACC/AHA guidelines downgraded aspirin to a Class IIb recommendation (may be considered) for primary prevention, representing a major shift from prior practice. 1, 2 This change was driven by three landmark 2018 trials—ASCEND, ARRIVE, and ASPREE—which collectively enrolled over 46,000 participants and found that aspirin's modest cardiovascular benefit was counterbalanced by increased bleeding risk. 1
The number needed to treat to cause major bleeding (210) is actually lower than the number needed to prevent an ASCVD event (265), indicating more harm than benefit in unselected populations. 1
Age-Based Recommendations
Adults Age 40-59 Years with ≥10% 10-Year ASCVD Risk
Low-dose aspirin (75-100 mg daily) might be considered only in highly select patients who meet ALL of the following criteria: 1, 2, 3
- Age 40-59 years with calculated 10-year ASCVD risk ≥10% 3
- Low bleeding risk (see contraindications below) 1, 2
- Willing to take daily aspirin long-term 1
- Presence of additional high-risk features such as: 1
- Current smoking
- Strong family history of premature ASCVD
- Very elevated cholesterol inadequately controlled with statins
- Coronary artery calcium score ≥100
- Chronic kidney disease/albuminuria 1
This decision requires shared decision-making that explicitly weighs the small cardiovascular benefit against the comparable bleeding risk. 1, 2
Adults Age 60-70 Years
Aspirin should generally NOT be initiated for primary prevention in this age group. 2, 3 The USPSTF 2022 recommendation statement concludes with moderate certainty that initiating aspirin in adults 60 years or older has no net benefit (Grade D recommendation). 3
Adults Over Age 70 Years
Aspirin should NOT be used for primary prevention in adults over 70 years. 1, 2, 3 The ASPREE trial specifically demonstrated increased risk of bleeding and death in this population, with no cardiovascular benefit. 1 Extended follow-up through 2025 showed a higher rate of MACE (HR 1.17) in those randomized to aspirin during the post-trial period, along with persistent increased bleeding risk (HR 1.24). 4
Absolute Contraindications to Aspirin
Do not prescribe aspirin for primary prevention if any of the following are present: 1, 2
- Prior gastrointestinal bleeding or active peptic ulcer disease
- Known bleeding disorder or thrombocytopenia
- Severe liver disease
- Concurrent anticoagulation (warfarin, DOACs)
- Regular NSAID use
- Uncontrolled hypertension
- Chronic kidney disease (increases bleeding risk)
- Age >70 years 1, 2
Special Population: Diabetes
Aspirin is NOT generally recommended for primary prevention in patients with diabetes. 1, 2 The ASCEND trial enrolled 15,480 diabetic patients without cardiovascular disease and found that while aspirin reduced serious vascular events by 12% (8.5% vs 9.6%), major bleeding increased by 29% (4.1% vs 3.2%). 1
For diabetic patients age ≥50 years with at least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or chronic kidney disease), aspirin may be considered only through shared decision-making if bleeding risk is low. 1
When Aspirin IS Strongly Indicated: Secondary Prevention
Aspirin 75-162 mg daily (most commonly 81 mg in the U.S.) remains strongly recommended for all patients with established ASCVD, where benefits far exceed bleeding risks. 1, 5, 2 This includes patients with prior myocardial infarction, stroke, or documented coronary artery disease. 5
Why the Paradigm Has Shifted
The contemporary evidence differs from older trials because: 1
- Modern populations have lower smoking rates
- Statin use is now widespread (34-75% in recent trials vs. minimal in older studies)
- Blood pressure control has improved substantially
- These evidence-based therapies reduce baseline cardiovascular risk, making aspirin's absolute benefit smaller while bleeding risk remains constant
Meta-regression analysis demonstrates that aspirin's treatment effect does NOT increase as ASCVD risk increases, contradicting the assumption that higher-risk patients derive greater benefit. 6
Practical Dosing When Aspirin Is Used
When aspirin is prescribed after careful risk-benefit assessment: 1, 5
- Use 75-100 mg daily (81 mg is the standard U.S. low-dose tablet) 1, 5
- No evidence supports doses above 162 mg for primary prevention 1
- Enteric-coated preparations do not clearly reduce gastrointestinal bleeding risk 5
Common Clinical Pitfalls to Avoid
Do not automatically prescribe aspirin based solely on a 10% 10-year ASCVD risk threshold—this outdated approach ignores the unfavorable risk-benefit ratio demonstrated in contemporary trials. 1, 2
Do not continue aspirin in patients who turn 70 years old without documented ASCVD—the risk-benefit ratio becomes unfavorable with age. 2, 4
Do not overlook bleeding risk factors when calculating net benefit—gastrointestinal bleeding risk may be as high as 5 per 1,000 per year in real-world settings. 1