What are the guidelines for aspirin (acetylsalicylic acid) therapy in patients with varying risk levels for cardiovascular events, including those with established cardiovascular disease, such as myocardial infarction or stroke, and those with contraindications or impaired renal function?

Aspirin Guidelines for Cardiovascular Disease Prevention

Secondary Prevention (Established Cardiovascular Disease)

For patients with established cardiovascular disease—including prior myocardial infarction, stroke, coronary revascularization, or documented obstructive coronary artery disease—aspirin 75-100 mg daily is mandatory for lifelong therapy, as the cardiovascular benefits far outweigh bleeding risks. 1, 2, 3

Specific Secondary Prevention Scenarios:

• Stable coronary artery disease (>1 year post-acute coronary syndrome): Use aspirin 75-162 mg daily as single antiplatelet therapy indefinitely 1, 2

• Acute coronary syndrome with stent placement:

  • First year: Dual antiplatelet therapy with aspirin 75-162 mg daily PLUS a P2Y12 inhibitor (ticagrelor 90 mg twice daily, clopidogrel 75 mg daily, or prasugrel 10 mg daily) 1, 3
  • After first year: Transition to aspirin monotherapy 75-100 mg daily indefinitely 1, 2

• Elective PCI with stent placement:

  • Bare-metal stent: Aspirin plus clopidogrel for minimum 1 month 1
  • Drug-eluting stent: Aspirin plus clopidogrel for 3-6 months 1
  • Consider continuing dual therapy up to 12 months for all stents 1

• Acute myocardial infarction: Loading dose of 160-325 mg immediately, then 75-162 mg daily long-term 1, 3

• Aspirin intolerance: Substitute clopidogrel 75 mg daily 2, 3

Primary Prevention (No Prior Cardiovascular Events)

Aspirin for primary prevention should be reserved for select patients aged 40-59 years with ≥10% 10-year cardiovascular risk and low bleeding risk, as recent evidence shows minimal benefit in lower-risk populations and potential harm in those ≥60 years. 2, 3

Primary Prevention Algorithm:

Age ≥60 years: Do NOT initiate aspirin for primary prevention regardless of cardiovascular risk 3

Age 50-59 years: Consider aspirin 75-100 mg daily IF:

• 10-year cardiovascular risk ≥10% AND
• Low bleeding risk AND
• Patient values preventing MI/stroke more than avoiding bleeding 1, 2

Age 40-49 years: May consider aspirin 75-100 mg daily only in very high-risk patients (10-year risk ≥10%) with low bleeding risk 2, 3

Age <40 years: Aspirin not recommended for primary prevention 1

Special Primary Prevention Populations:

• Diabetes mellitus (age ≥50 years): Consider aspirin 75-162 mg daily if ≥1 additional major risk factor present (hypertension, dyslipidemia, smoking, family history of premature ASCVD, chronic kidney disease, or albuminuria) AND low bleeding risk 2, 3

• Hypertension: Aspirin 75-81 mg daily may be considered if age ≥50 years with controlled blood pressure (<150/90 mmHg), target organ damage or diabetes, and 10-year cardiovascular risk >10-15% 2

• Women for stroke prevention: Aspirin 81 mg daily or 100 mg every other day may be reasonable when 10-year stroke risk is sufficiently high (≥6-10%) to outweigh bleeding risks 2

Absolute Contraindications to Aspirin

Aspirin is contraindicated in patients with: 2, 3

• Active bleeding or recent gastrointestinal bleeding
• Known bleeding disorder or thrombocytopenia
• Documented aspirin allergy
• Concurrent anticoagulation therapy (warfarin, DOACs)
• Age <21 years (Reye syndrome risk)
• Uncontrolled hypertension (increases hemorrhagic stroke risk)

High Bleeding Risk Factors (Relative Contraindications)

Exercise extreme caution or avoid aspirin in patients with: 1, 2, 3

• History of peptic ulcer disease or gastrointestinal bleeding
• Concurrent NSAID or corticosteroid use
• Chronic kidney disease (creatinine >2.0-2.5 mg/dL)
• Age ≥70 years (bleeding risk substantially increases)
• Anemia
• Thrombocytopenia

Optimal Dosing Strategy

The most appropriate dose for both primary and secondary prevention is 75-100 mg daily (81 mg in the US), as this provides complete platelet inhibition with the lowest bleeding risk. 1, 2, 3

Dosing by Clinical Scenario:

• Long-term prevention (primary or secondary): 75-100 mg daily 1, 2, 3
• Acute coronary syndrome: Loading dose 160-325 mg, then 75-100 mg daily 3
• Acute ischemic stroke: Loading dose 160-300 mg, then 75-100 mg daily 3
• During dual antiplatelet therapy: Use lowest dose (75-81 mg) to minimize bleeding risk 4

Important caveat: Higher doses (>100 mg daily) provide NO additional cardiovascular benefit but significantly increase bleeding complications, particularly gastrointestinal bleeding 5, 4. The ADAPTABLE trial confirmed that 81 mg and 325 mg daily have equivalent efficacy but 81 mg has better safety 2.

Bleeding Risk Quantification

The absolute bleeding risk with aspirin therapy is: 1, 2

• Major gastrointestinal bleeding: 2-4 per 1,000 middle-aged persons over 5 years (4-12 per 1,000 in elderly)
• Hemorrhagic stroke: 0-2 per 1,000 persons over 5 years
• Fatal bleeding: Rare, similar across doses of 75-162 mg daily

Special Considerations for Renal Impairment

While the provided guidelines don't extensively address aspirin dosing in renal impairment specifically, general principles apply: 1

• Monitor renal function (creatinine should be <2.5 mg/dL in men, <2.0 mg/dL in women for optimal safety)
• Chronic kidney disease increases bleeding risk substantially
• Consider dose reduction or avoidance in severe renal impairment (CrCl <30 mL/min)

Common Pitfalls to Avoid

• Do not use aspirin for primary prevention in low-risk patients (age <50 years without multiple risk factors)—bleeding risks exceed minimal benefits 2, 3

• Do not use higher doses thinking they provide better protection—doses >100 mg daily increase bleeding without improving efficacy 5, 4

• Do not initiate aspirin in patients ≥60 years for primary prevention—recent evidence shows net harm in this age group 3

• Do not forget to control blood pressure before starting aspirin—uncontrolled hypertension dramatically increases hemorrhagic stroke risk 2

• Do not combine aspirin with NSAIDs or anticoagulants without careful risk-benefit assessment—this substantially increases major bleeding risk 1, 2

• Gender differences matter in primary prevention: Aspirin reduces MI in men but not women, while reducing stroke in women but not men 2, 3