What is the recommended aspirin (acetylsalicylic acid) dosage and duration for secondary prevention in patients with a history of cardiovascular disease?

Aspirin for Secondary Prevention in Cardiovascular Disease

For patients with established cardiovascular disease, use low-dose aspirin 75-100 mg daily indefinitely as lifelong monotherapy after the initial 12-month period following an acute event. 1

Dosing Recommendations

Standard Maintenance Dose

• 75-100 mg daily is the recommended dose for long-term secondary prevention in patients with established coronary artery disease (defined as >1 year post-acute coronary syndrome, prior revascularization, coronary stenoses >50%, or evidence of cardiac ischemia) 1
• The American Heart Association supports 75-162 mg daily for secondary prevention in patients with atherosclerotic cardiovascular disease 1
• European guidelines recommend aspirin for chronic phase (>12 months) after myocardial infarction as Class I, Level A evidence 1

Acute Loading Dose

• 162-325 mg loading dose (chewed, non-enteric coated) for acute coronary syndromes, followed by maintenance dosing 2
• The loading dose should be administered even in patients already on aspirin therapy 2

Duration of Therapy

Single vs. Dual Antiplatelet Therapy Timeline

First 12 months after acute coronary syndrome:

• Dual antiplatelet therapy (aspirin + P2Y12 inhibitor) is recommended for the first year following ACS 1
• Preferred P2Y12 inhibitors: ticagrelor 90 mg twice daily or prasugrel 10 mg daily over clopidogrel 75 mg daily 1
• For patients who cannot receive ticagrelor or prasugrel, use clopidogrel 75 mg daily 1

After stent placement (elective PCI):

• Bare-metal stents: minimum 1 month of dual antiplatelet therapy 1
• Drug-eluting stents: 3-6 months of dual antiplatelet therapy (3 months for -limus stents, 6 months for -taxel stents) 1
• Consider continuation to 12 months, then transition to monotherapy 1

Beyond 12 months:

• Single antiplatelet therapy (aspirin 75-100 mg daily) is recommended over continuation of dual therapy 1
• This represents lifelong therapy for secondary prevention 1

Alternative Antiplatelet Agents

For aspirin allergy or intolerance:

• Clopidogrel 75 mg daily is the recommended alternative 1, 3
• This is a Class I, Level A recommendation for patients with documented aspirin allergy 3
• Rapid desensibilization protocols exist (starting with 40.5 mg, increasing to 81 mg after 90 minutes) but require medical supervision 2

Aspirin vs. clopidogrel monotherapy:

• Both are acceptable for long-term secondary prevention in stable disease 1
• Clopidogrel showed slight superiority in the CAPRIE trial (5.32% vs 5.83% annual event rate, P=0.043) but with similar bleeding rates 1

Special Populations

Patients with Diabetes

• Aspirin 75-162 mg daily is recommended for secondary prevention in diabetic patients with established atherosclerotic cardiovascular disease 1
• The benefit clearly outweighs bleeding risk in this population 1

Cerebrovascular Disease

• For non-cardioembolic stroke/TIA: either dipyridamole plus aspirin OR clopidogrel alone (both Class I, Level A) 1
• If intolerance to dipyridamole or clopidogrel, aspirin alone is recommended 1
• Anticoagulation is not superior to aspirin and is not recommended 1

Critical Safety Considerations

Bleeding Risk

• Major bleeding increases by approximately 5 per 1,000 patients per year, predominantly gastrointestinal 1, 2
• The bleeding risk is dose-dependent, with doses >325 mg daily carrying higher risk 4, 5
• Despite bleeding risk, the mortality and morbidity benefits in secondary prevention far outweigh harms 1, 6

Risk Mitigation

• Use the lowest effective dose (75-100 mg) to minimize bleeding while maintaining efficacy 1, 5
• Consider proton pump inhibitor co-therapy in high-risk patients (history of GI bleeding, concurrent NSAID use, anticoagulation) 3
• Avoid non-enteric coated formulations for loading doses to ensure rapid absorption 2

Common Pitfalls to Avoid

1. Never discontinue aspirin abruptly in stable CAD patients without compelling contraindication (active bleeding) 1

2. Do not continue dual antiplatelet therapy beyond 12 months in stable patients - this increases bleeding without reducing ischemic events 1, 3

3. Do not use aspirin doses >325 mg daily for chronic therapy - higher doses increase bleeding without improving efficacy 1, 4, 5

4. Never add clopidogrel to aspirin for routine bleeding management (e.g., hematuria) - this worsens hemorrhage risk 3

5. Do not use aspirin as primary prevention in low-risk individuals - bleeding risk outweighs benefit 1

Monitoring and Follow-up

• No routine laboratory monitoring is required for aspirin therapy 3
• Assess adherence regularly, as non-adherence is common and undermines benefit 1
• Watch for signs of bleeding (melena, hematemesis, unexplained anemia) 2
• Approximately 10-20% of patients may have high on-treatment platelet reactivity ("aspirin resistance"), though routine testing is not currently recommended 7