What are the indications and dosing guidelines for aspirin (acetylsalicylic acid) therapy?

Aspirin Therapy: Indications and Dosing

Aspirin is strongly recommended for secondary prevention in all patients with established atherosclerotic cardiovascular disease (ASCVD) at 75-100 mg daily, while for primary prevention it should only be considered in select high-risk patients aged 40-59 years with ≥10% 10-year CVD risk after careful assessment of bleeding risk, and is generally not recommended in adults ≥70 years or those <50 years without multiple risk factors. 1, 2

Secondary Prevention Indications (Strong Recommendations)

Aspirin 75-100 mg daily is definitively indicated for:

• Acute myocardial infarction: Loading dose of 160-325 mg initially, followed by 75-150 mg daily long-term 3, 2
• Prior myocardial infarction or revascularization: 75-100 mg daily as lifelong therapy after initial dual antiplatelet therapy (DAPT) period 1, 2
• Stable or unstable angina: 75-100 mg daily 3, 2
• Prior stroke or transient ischemic attack: 75-100 mg daily 3, 2
• Documented ASCVD on imaging: 75-100 mg daily for patients with significant obstructive coronary artery disease 1

The benefits of aspirin in secondary prevention far outweigh bleeding risks, making it uniformly recommended in these populations. 3, 1

Acute Coronary Syndromes - Special Dosing

• Minor ischemic stroke (NIHSS ≤3) or high-risk TIA: Dual antiplatelet therapy with aspirin 81 mg plus clopidogrel 75 mg daily, initiated within 12-24 hours with loading doses (aspirin 160-325 mg, clopidogrel 300-600 mg), continued for 21 days, then transition to single antiplatelet therapy 3
• Post-ACS patients: Aspirin plus P2Y12 inhibitor for at least 1 year, with evidence supporting ticagrelor or clopidogrel depending on whether percutaneous coronary intervention was performed 3, 1

Primary Prevention Indications (Selective Use)

Adults Aged 40-59 Years

Aspirin 75-162 mg daily may be considered for primary prevention in adults aged 40-59 years with ≥10% 10-year CVD risk who are not at increased bleeding risk, using shared decision-making. 4, 1

Diabetes-Specific Recommendations

Aspirin 75-162 mg daily may be reasonable for:

• Men and women ≥50 years with diabetes PLUS at least one additional major risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or chronic kidney disease/albuminuria) who are not at increased bleeding risk 3, 1

Clinical judgment is required for intermediate-risk patients (younger patients with one or more risk factors or older patients without risk factors). 3

Pregnancy - Preeclampsia Prevention

Low-dose aspirin is recommended for preeclampsia prevention in pregnant women with:

• One "high" risk factor OR at least two "moderate" risk factors: Dosing ranges from 75-162 mg daily, initiated optimally before 16 weeks gestation (definitely by 12-20 weeks), continued until delivery or 35-37 weeks depending on guideline 3
• High risk factors include chronic hypertension, pre-gestational diabetes, antiphospholipid antibody syndrome, previous preeclampsia, chronic kidney disease, and systemic lupus 3

Populations Where Aspirin is NOT Recommended

Aspirin should not be used in the following groups due to bleeding risks outweighing minimal benefits:

• Adults ≥70 years for primary prevention: Greater risk than benefit in this age group 3, 1
• Adults <50 years with diabetes and no other major ASCVD risk factors: Low benefit outweighed by bleeding risks 3, 1
• Patients <21 years: Contraindicated due to Reye syndrome risk 3, 1
• Low cardiovascular risk individuals: Men and women without established CVD and low 10-year risk 1, 2

Dosing Guidelines

Standard Maintenance Doses

• Secondary prevention: 75-100 mg daily (81 mg is the most common U.S. formulation) 3, 1, 2
• Primary prevention: 75-162 mg daily when indicated 3, 1
• Acute MI loading dose: 160-325 mg initially 3, 2

Using the lowest effective dose (75-81 mg) minimizes bleeding risk while maintaining efficacy. 3, 1

Dose Range Evidence

Clinical trials in diabetes patients used doses ranging from 50-650 mg daily, but most were in the 100-325 mg/day range, with little evidence supporting any specific dose advantage for higher doses 3

Bleeding Risk Assessment

Risk Factors for Increased Bleeding

• Age >70 years 3, 2
• Anemia 3
• Renal disease 3
• Uncontrolled hypertension 1, 2
• Concomitant use of NSAIDs or anticoagulants 1, 2
• History of gastrointestinal bleeding 2

Quantifying Risk-Benefit

• Gastrointestinal bleeding risk: Increases by relative risk 1.6, with absolute rates of 2-4 per 1,000 middle-aged persons (4-12 per 1,000 older persons) over 5 years 1
• Hemorrhagic stroke risk: May increase by 0-2 per 1,000 persons over 5 years 1
• In patients with ASCVD risk >1% per year: Number of cardiovascular events prevented equals or exceeds bleeding episodes induced 3, 1, 2

Alternative Antiplatelet Therapy

For patients with documented aspirin allergy or intolerance, clopidogrel 75 mg daily is the recommended alternative. 1, 2

Common Pitfalls to Avoid

• Do not prescribe aspirin for primary prevention in patients ≥70 years: The balance clearly favors harm over benefit in this age group 3, 1
• Do not use aspirin in patients with uncontrolled hypertension: Control blood pressure first to minimize bleeding risk 1
• Do not assume higher doses are better: Doses >100 mg increase side effects without improving efficacy for long-term use 3, 1
• Do not use aspirin as a substitute for managing other cardiovascular risk factors: It should be an adjunct to comprehensive risk factor management 5