Aspirin for Primary Prevention in Elevated ASCVD Risk: Generally Not Recommended
Aspirin is generally NOT recommended for primary prevention in patients with elevated ASCVD risk, as recent evidence demonstrates that bleeding risks equal or exceed cardiovascular benefits in the contemporary era of optimized statin and antihypertensive therapy. 1
Current Guideline Recommendations
The 2019 ACC/AHA guidelines downgraded aspirin to a Class IIb recommendation (may be considered, not routinely recommended) for primary prevention, reflecting the unfavorable risk-benefit ratio in modern practice 1:
- Low-dose aspirin (75-100 mg daily) might be considered only for highly select adults aged 40-70 years at higher ASCVD risk who are NOT at increased bleeding risk 1
- Aspirin should NOT be used routinely in adults >70 years of age (Class III: Harm) 1
- Aspirin should NOT be used in any adult at increased bleeding risk (Class III: Harm) 1
Why the Shift Away from Aspirin?
Recent large trials (ASCEND, ASPREE, ARRIVE) demonstrate that aspirin's modest cardiovascular benefit is offset by comparable bleeding risk when patients receive contemporary evidence-based therapies 1, 2:
- The ASCEND trial in 15,480 diabetic patients showed only a 12% reduction in cardiovascular events (8.5% vs 9.6%), but a 29% increase in major bleeding (4.1% vs 3.2%) 1
- The number of ASCVD events prevented equals the number of bleeding episodes induced in patients with >1% annual ASCVD risk 1
- Meta-regression analysis found no relationship between baseline ASCVD risk and aspirin's treatment effect—meaning higher risk does NOT translate to greater benefit 3
Specific Populations Where Aspirin Should Be Avoided
Age >70 Years
- Greater bleeding risk than cardiovascular benefit regardless of ASCVD risk 1
- The ASPREE trial confirmed net harm in elderly populations 2
Increased Bleeding Risk Factors
Aspirin is contraindicated in patients with 1:
- History of gastrointestinal bleeding or peptic ulcer disease
- Thrombocytopenia or coagulopathy
- Chronic kidney disease
- Concurrent use of NSAIDs, steroids, anticoagulants, or other bleeding-risk medications
Low-Risk Patients
- Adults <50 years without additional major risk factors should NOT receive aspirin 1
- The low absolute benefit is outweighed by bleeding risks 1
When Aspirin IS Clearly Indicated: Secondary Prevention
Aspirin (75-162 mg daily) remains strongly recommended for secondary prevention in patients with established ASCVD, where benefits far exceed risks 1:
- Documented coronary artery disease
- Prior myocardial infarction
- Prior ischemic stroke
- Peripheral arterial disease
The ADAPTABLE trial showed no difference in outcomes between 81 mg and 325 mg daily dosing, supporting use of the lowest effective dose (81 mg in the U.S.) 1
Special Consideration: Diabetes
For diabetic patients, the 2022 American Diabetes Association guidelines state 1:
- Aspirin is NOT generally recommended for primary prevention
- May be considered only in the context of shared decision-making for patients at high cardiovascular risk with low bleeding risk
- Even in diabetes with multiple risk factors, the cardiovascular benefits are "fairly comparable" to bleeding risks 1
Common Pitfalls to Avoid
- Do not use the 10% 10-year ASCVD risk threshold as an automatic indication for aspirin—this outdated approach from older guidelines no longer applies given recent trial data 1
- Do not assume higher ASCVD risk justifies aspirin use—the treatment effect does not increase with baseline risk 3
- Do not overlook bleeding risk factors when calculating net benefit—bleeding risk correlates poorly with ASCVD risk 1
- Do not continue aspirin in patients >70 years without documented ASCVD, even if previously started 1