Antiplatelet Therapy in Primary Prevention
Aspirin cannot be recommended for primary prevention in patients without established cardiovascular disease due to increased major bleeding risk that equals or exceeds the modest reduction in cardiovascular events. 1
Evidence Against Routine Primary Prevention
The European Society of Cardiology explicitly states that aspirin cannot be recommended in primary prevention due to its increased risk of major bleeding, even in individuals with multiple cardiovascular risk factors 1. This recommendation is based on systematic review data showing that while aspirin reduces serious vascular events from 0.57% to 0.51% per year (a modest 12% relative risk reduction), this benefit is offset by increased hemorrhagic complications 1.
Recent large-scale trials have reinforced this position:
- ARRIVE trial (12,546 patients): No benefit on primary endpoints (4.29% vs 4.48%, HR 0.96, p=0.60), with doubled gastrointestinal bleeding risk (0.97% vs 0.46%, HR 2.11) 1
- ASPREE trial (19,114 elderly patients): No cardiovascular benefit (HR 0.95), but 38% increased major hemorrhage rate (8.6 vs 6.2 events per 1,000 person-years, HR 1.38) 1
The absolute bleeding risk approximates 5 per 1,000 patients per year, which equals or exceeds the number of cardiovascular events prevented in primary prevention populations 1, 2.
Limited Exceptions for Selective Use
Aspirin 75-162 mg daily may be considered only in highly selected patients with diabetes who meet ALL of the following criteria: 1
- Age 50-70 years (not >70 years due to excessive bleeding risk)
- At least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or chronic kidney disease/albuminuria)
- Low bleeding risk (no history of gastrointestinal bleeding, no anemia, no renal disease, not on anticoagulation or NSAIDs)
- 10-year ASCVD risk ≥10%
The American Diabetes Association emphasizes this is a "may be considered" recommendation (not a strong recommendation), reflecting the marginal benefit-to-risk ratio even in this higher-risk subgroup 1.
Clopidogrel Has No Role in Primary Prevention
The CHARISMA trial demonstrated that clopidogrel added to aspirin provides no significant benefit in individuals with multiple risk factors but no established cardiovascular disease 1. Clopidogrel monotherapy has not been adequately studied for primary prevention and should not be used 3.
Critical Pitfalls to Avoid
- Do not prescribe aspirin for primary prevention in patients >70 years old, as bleeding risk substantially exceeds any cardiovascular benefit in this age group 1
- Do not use aspirin in patients with uncontrolled hypertension until blood pressure is adequately controlled, as this markedly increases hemorrhagic stroke risk 2
- Do not combine aspirin with anticoagulation or NSAIDs in primary prevention, as bleeding risk becomes prohibitive 2
- Do not assume diabetes alone justifies aspirin - multiple additional risk factors and low bleeding risk are required 1
When Antiplatelet Therapy IS Indicated
Aspirin 75-100 mg daily is strongly recommended for secondary prevention in patients with established atherosclerotic cardiovascular disease (prior myocardial infarction, stroke, peripheral arterial disease, or documented coronary stenosis >50%) 1, 2, 3. In this population, the absolute cardiovascular benefit (13-37 fewer events per 1,000 treated) substantially outweighs bleeding risk 1.
For patients with documented aspirin allergy in secondary prevention, clopidogrel 75 mg daily should be substituted 1, 2.