What antiplatelet therapy (agents, dosing, and duration) is recommended for secondary prevention of myocardial infarction, ischemic stroke, and peripheral arterial disease, including dual antiplatelet therapy after acute coronary syndrome or coronary stenting?

Antiplatelet Therapy for Secondary Prevention

Standard Monotherapy for Established Disease

For patients with established coronary artery disease (≥1 year post-MI, prior revascularization, or documented stenosis >50%), aspirin 75-100 mg daily is the cornerstone of lifelong secondary prevention, reducing the combined risk of non-fatal MI, non-fatal stroke, and vascular death by approximately 20-30%. 1, 2

• Clopidogrel 75 mg daily is an equally effective alternative for patients with aspirin intolerance, allergy, or contraindication 1, 3
• For ischemic stroke survivors, either aspirin 75-100 mg daily, clopidogrel 75 mg daily, or aspirin plus extended-release dipyridamole are acceptable first-line options 1
• In peripheral arterial disease, clopidogrel 75 mg daily is preferred over aspirin based on superior efficacy in this population 4

---

Dual Antiplatelet Therapy After Acute Coronary Syndrome

Initial 12-Month Period (Class I Recommendation)

All patients with acute coronary syndrome (NSTE-ACS or STEMI) must receive dual antiplatelet therapy with aspirin 75-100 mg daily PLUS a P2Y12 inhibitor for 12 months, regardless of whether they underwent PCI, received fibrinolysis, or were managed medically. 1, 5

P2Y12 inhibitor selection hierarchy:

1. Ticagrelor 90 mg twice daily is preferred over clopidogrel (Class IIa recommendation) based on superior reduction in cardiovascular death, MI, and stroke 1, 5

2. Prasugrel 10 mg daily (5 mg if weight <60 kg or age ≥75 years) is reasonable over clopidogrel in patients WITHOUT prior stroke/TIA and NOT at high bleeding risk 1

   • Prasugrel is absolutely contraindicated (Class III: Harm) in patients with prior stroke or TIA due to increased intracranial hemorrhage risk (6.5% vs 1.2%) 1, 5

3. Clopidogrel 75 mg daily (with 300-600 mg loading dose) is appropriate when ticagrelor or prasugrel cannot be used 1, 3

After 12 Months: Transition Strategy

At 12 months post-ACS, transition to aspirin 75-100 mg daily monotherapy indefinitely (Class I, Level A recommendation). 1, 5, 2

• Clopidogrel 75 mg daily is an acceptable alternative for lifelong monotherapy if aspirin is not tolerated 5, 2

---

Extended DAPT Beyond 12 Months (Selective Use)

Extended DAPT may be reasonable (Class IIb) ONLY in patients who meet ALL three criteria: 1, 5

1. Tolerated initial 12 months of DAPT without bleeding complications
2. NOT at high bleeding risk (no history of intracranial hemorrhage, recent major bleeding, chronic kidney disease requiring dialysis, severe liver disease, or thrombocytopenia)
3. High ischemic risk features present:
   • Diabetes mellitus requiring medication 1, 5
   • History of recurrent MI 1, 5
   • Multivessel coronary disease 1, 5
   • Chronic kidney disease with eGFR 15-59 mL/min/1.73 m² 1, 5
   • Complex PCI (≥3 stents, total stent length >60 mm, left main or bifurcation stenting, chronic total occlusion) 1
   • Prior stent thrombosis on antiplatelet therapy 1
   • Polyvascular disease (CAD plus PAD) 1, 5

If extended DAPT is chosen, use ticagrelor 60 mg twice daily (reduced dose) plus aspirin 75-100 mg daily for up to 36 months. 1, 5

• This regimen reduces cardiovascular death, MI, or stroke by 1.2-1.3% absolute risk but increases major bleeding by 1.2-1.5% 5
• Alternative extended regimens include clopidogrel 75 mg daily or prasugrel 10 mg daily (5 mg if applicable) plus aspirin, though ticagrelor 60 mg is preferred 1

---

DAPT After Elective PCI with Stenting (Chronic Coronary Syndrome)

For elective PCI in stable coronary disease, DAPT duration is shorter than post-ACS: 1

• Bare-metal stents: Aspirin plus clopidogrel for minimum 1 month, ideally up to 12 months (Class 1A) 1, 3
• Drug-eluting stents: Aspirin plus clopidogrel for 3-6 months (Class 1A) 1
• After completing the initial DAPT period, transition to aspirin 75-100 mg daily monotherapy indefinitely 1

---

Peripheral Arterial Disease

For symptomatic PAD, clopidogrel 75 mg daily is preferred over aspirin as monotherapy. 3, 4

For PAD patients at high ischemic risk with low bleeding risk, consider adding rivaroxaban 2.5 mg twice daily to aspirin 75-100 mg daily (dual pathway inhibition). 1

• This combination reduces major adverse cardiovascular events with NNT of 77 but increases bleeding with NNH of 84 1

---

Critical Dosing Details

• Aspirin maintenance dose during DAPT: 75-100 mg daily (NOT 325 mg) to minimize bleeding without compromising efficacy 1, 5
• Aspirin after CABG: 100-325 mg daily for 1 year to reduce saphenous vein graft closure, then reduce to 75-100 mg daily 2
• Clopidogrel loading dose in ACS: 300-600 mg 1, 3

---

Common Pitfalls to Avoid

1. Never discontinue ALL antiplatelet therapy after completing DAPT – this is the most dangerous error; always continue aspirin or clopidogrel monotherapy indefinitely 5, 2

2. Never use prasugrel in patients with prior stroke/TIA at any timepoint – absolute contraindication due to cerebrovascular bleeding risk 1, 5

3. Never continue DAPT beyond 12 months in patients with high bleeding risk – bleeding harm outweighs ischemic benefit 1

4. Never use aspirin >100 mg daily during or after DAPT – higher doses increase bleeding without improving efficacy 5

5. Never use dual antiplatelet therapy within 3 months after ischemic stroke or TIA (Class III: No Benefit) unless it was a minor stroke with high-risk TIA where short-term DAPT is specifically indicated 3

6. Discontinue clopidogrel 5 days before elective surgery with major bleeding risk, resume when hemostasis achieved 3

7. Never use oral anticoagulation instead of antiplatelet therapy for atherosclerotic disease unless there is a separate indication (e.g., atrial fibrillation) 3, 2