Aspirin 325mg for Cardiovascular Prophylaxis
For long-term cardiovascular prophylaxis, aspirin 81mg (75-100mg) daily is the appropriate dose, not 325mg—higher doses provide no additional cardiovascular protection but significantly increase bleeding risk. 1, 2
Evidence-Based Dosing Recommendations
Maintenance Therapy for Established Cardiovascular Disease
The optimal maintenance dose is 75-100mg daily for patients with established atherosclerotic cardiovascular disease, as recommended by the American Diabetes Association and European Society of Cardiology 2
The 2025 ACC/AHA guidelines specifically recommend 75-100mg daily for maintenance therapy after the initial 30-day period following acute coronary syndrome 1
The American College of Chest Physicians found no convincing evidence that doses above 162mg are more effective than lower doses for preventing serious vascular events 2
When 325mg Dosing Is Appropriate
The 325mg dose should only be used as a loading dose in acute situations, not for chronic prophylaxis:
Loading dose of 162-325mg non-enteric coated aspirin (chewed when possible) is indicated for acute coronary syndromes, myocardial infarction, or before percutaneous coronary intervention 1, 2
After carotid endarterectomy, 81-325mg daily is acceptable initially, but lower doses within this range are preferred for long-term use 1
Following the acute phase (first 30 days), transition to 75-100mg daily for maintenance therapy 1, 2
Bleeding Risk with Higher Doses
The evidence clearly demonstrates dose-dependent harm without additional benefit:
Gastrointestinal side effects are clearly dose-dependent, with 325mg causing significantly more GI symptoms than 81mg 2
The ADAPTABLE trial (>15,000 patients) found no difference in cardiovascular events between 81mg and 325mg, but confirmed increased bleeding with higher doses 2
Long-term use of 325mg increases bleeding risk without providing additional cardiovascular protection compared to 75-100mg 3, 4
Major bleeding occurs at approximately 5 excess events per 1,000 patients per year with any aspirin dose, making the lowest effective dose imperative 2
Clinical Algorithm for Aspirin Dosing
For acute presentation (Day 1):
- Give 162-325mg non-enteric coated aspirin immediately (chewed) 1, 2
- Continue 162-325mg daily for up to 30 days post-PCI or acute event 1
For maintenance therapy (after 30 days):
- Transition to 75-100mg (typically 81mg) daily indefinitely 1, 2
- Use non-enteric coated formulation for better absorption 1
Special consideration with ticagrelor:
- When using ticagrelor as the P2Y12 inhibitor, aspirin doses must not exceed 100mg daily due to reduced efficacy observed with higher doses in the PLATO trial 1
Common Pitfalls to Avoid
Do not continue 325mg for chronic prophylaxis after the initial acute phase—this is a widespread error that increases bleeding without benefit 2, 4
Do not assume "more is better"—pharmacodynamic data show that doses as low as 30mg daily fully inhibit platelet thromboxane production 4
Do not use enteric-coated aspirin for acute situations—non-enteric coated formulations achieve faster platelet inhibition 1
In the United States, 325mg is commonly prescribed (35% of cases) despite evidence supporting lower doses—this represents inappropriate prescribing 4
Supporting Evidence from Multiple Guidelines
The convergence of evidence across multiple high-quality guidelines is striking:
The 2011 ACC/AHA carotid disease guidelines recommend 81-325mg with preference for lower doses for long-term prophylaxis 1
The 2014 AHA/ACC NSTE-ACS guidelines specify 81-325mg post-PCI, with 81mg preferred long-term 1
The 2025 ACC/AHA acute coronary syndrome guidelines explicitly state 75-100mg for maintenance therapy 1
The American College of Chest Physicians recommends 75-100mg as optimal maintenance dose 1, 2
Bottom line: Prescribing 325mg aspirin for chronic cardiovascular prophylaxis is outdated practice that exposes patients to unnecessary bleeding risk. Use 81mg (75-100mg) daily for maintenance therapy. 1, 2, 4