What is the recommended dosage and timing of aspirin (acetylsalicylic acid) for cardiovascular protection?

Aspirin Dosing and Timing for Cardiovascular Protection

For established cardiovascular disease (secondary prevention), use aspirin 75-100 mg once daily indefinitely; for primary prevention in select high-risk patients aged ≥50 years, use 75-100 mg daily, but generally avoid in those >70 years or at low cardiovascular risk due to bleeding concerns outweighing benefits. 1

Secondary Prevention (Established Cardiovascular Disease)

Aspirin is strongly recommended for all patients with documented atherosclerotic cardiovascular disease (ASCVD), including those with prior myocardial infarction, stroke, revascularization, or significant coronary stenosis. 1

Dosing for Secondary Prevention:

• Daily dose: 75-100 mg is optimal for long-term secondary prevention 1
• The most common U.S. formulation is 81 mg daily 1
• No difference in cardiovascular outcomes or major bleeding between 81 mg and 325 mg daily in the ADAPTABLE trial, supporting use of the lower dose to minimize side effects 1
• Doses ranging from 75-162 mg/day appear optimal based on current evidence 1

Acute Settings Requiring Loading Doses:

• For acute coronary syndromes or acute ischemic stroke: give 160-300 mg loading dose at diagnosis to achieve rapid platelet inhibition 1
• After the acute phase, transition to maintenance dose of 75-100 mg daily 1

Duration:

• Lifelong therapy is recommended for secondary prevention 1, 2
• After the first year post-acute coronary syndrome or post-stenting, continue single antiplatelet therapy (aspirin alone) rather than dual therapy 1

Primary Prevention (No Prior Cardiovascular Events)

The benefit-risk balance for primary prevention is far less favorable than secondary prevention, requiring careful patient selection. 1

Who Should Receive Aspirin for Primary Prevention:

• Consider in patients aged ≥50 years with diabetes PLUS at least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, chronic kidney disease/albuminuria) who are NOT at increased bleeding risk 1, 2
• May consider in those with 10-year cardiovascular risk ≥10% when benefits likely outweigh bleeding risks 1, 2
• Requires shared decision-making weighing modest cardiovascular benefit against comparable bleeding risk 1

Who Should NOT Receive Aspirin for Primary Prevention:

• Patients aged <50 years with diabetes and no other major ASCVD risk factors - bleeding risk outweighs minimal benefit 1
• Patients aged >70 years - greater bleeding risk than cardiovascular benefit in this age group 1
• Patients aged <21 years - contraindicated due to Reye syndrome risk 1
• Low cardiovascular risk individuals (10-year risk <6-10%) - very small absolute benefit offset by bleeding complications 1

Dosing for Primary Prevention:

• 75-100 mg daily is the recommended dose range 1
• In the U.S., 81 mg daily is most commonly used 1

Dual Antiplatelet Therapy (Aspirin + P2Y12 Inhibitor)

Dual antiplatelet therapy is indicated after acute coronary syndromes and percutaneous coronary intervention with stenting. 1

Post-Acute Coronary Syndrome:

• First year after ACS: aspirin 75-100 mg daily PLUS ticagrelor 90 mg twice daily (preferred) or clopidogrel 75 mg daily 1
• Ticagrelor is suggested over clopidogrel based on superior outcomes 1

Post-Stenting:

• Bare-metal stents: minimum 1 month of dual therapy 1
• Drug-eluting stents: minimum 3-6 months of dual therapy 1
• Consider continuing dual therapy for 12 months for all stent types 1
• After 12 months: transition to single antiplatelet therapy (aspirin alone) 1

Timing of Administration

Standard recommendation is once-daily dosing, typically in the morning, though emerging evidence suggests timing may matter. 1

• Most guidelines recommend once-daily administration without specifying time of day 1
• One study found that morning dosing resulted in lower platelet inhibition during early morning hours (when cardiovascular events peak) compared to evening or twice-daily dosing 3
• However, no clinical outcome trials have demonstrated superiority of evening versus morning dosing, so standard once-daily dosing (typically morning) remains appropriate 3

Key Bleeding Risk Considerations

Major bleeding risk with low-dose aspirin is approximately 1-2 events per 1,000 patient-years in low-risk populations, potentially up to 5 per 1,000 in real-world settings. 1, 4

Contraindications and High-Risk Situations:

• Active gastrointestinal bleeding or recent bleeding history 1, 2
• Uncontrolled hypertension (increases bleeding risk) 1, 2
• Concurrent anticoagulant therapy or other NSAIDs (amplifies bleeding risk) 1, 2
• Severe thrombocytopenia (platelets <50,000/μL) 4
• Aspirin allergy or intolerance 1, 2
• Clinically active hepatic disease 2

For Patients with Aspirin Intolerance:

• Clopidogrel 75 mg daily is the recommended alternative for secondary prevention 1, 4

Common Pitfalls to Avoid

• Do not use higher doses than necessary - doses above 100 mg daily increase bleeding risk without additional cardiovascular benefit 1, 4
• Do not prescribe aspirin for primary prevention in low-risk individuals - the bleeding risk exceeds the minimal cardiovascular benefit 1
• Do not continue dual antiplatelet therapy beyond recommended duration without specific indication - increases bleeding risk unnecessarily 1
• Do not assume "aspirin resistance" requires higher doses - no evidence supports empirically increasing aspirin doses based on platelet function testing 1
• Do not routinely add proton pump inhibitors to low-dose aspirin (75-100 mg) - insufficient evidence for this strategy 1