What are the primary indications for antiplatelet therapy in patients with a history of cardiovascular disease, such as myocardial infarction, stroke, or peripheral artery disease?

Primary Indications for Antiplatelet Therapy

Antiplatelet therapy is indicated to reduce the risk of myocardial infarction, stroke, and vascular death in patients with symptomatic atherosclerotic cardiovascular disease, including those with recent MI, recent stroke, peripheral artery disease, or acute coronary syndromes. 1

Core Indications for Single Antiplatelet Therapy

Established Atherosclerotic Disease (Class I Recommendation)

• Symptomatic peripheral artery disease including claudication, critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia 1

• Recent myocardial infarction - aspirin 75-325 mg daily reduces vascular death by 23% and non-fatal vascular events by 50% when started within 24 hours 1

• Recent ischemic stroke or transient ischemic attack - antiplatelet therapy reduces serious vascular events by 36 per 1000 patients treated for 2 years 1

• Chronic stable angina - aspirin 75 mg daily reduces myocardial infarction or sudden death by 34% over 50 months of follow-up 1

Asymptomatic Disease (Class IIa Recommendation)

• Asymptomatic PAD with ABI ≤0.90 - single antiplatelet therapy is reasonable to reduce the risk of major adverse cardiovascular events 1

• Note: For borderline ABI (0.91-0.99), the usefulness of antiplatelet therapy remains uncertain 1

Agent Selection Algorithm

First-Line Options

Aspirin 75-325 mg daily (Level of Evidence: A for symptomatic PAD; B for recent MI/stroke) 1

• Most cost-effective option
• Proven efficacy across all cardiovascular disease states
• Doses of 75-100 mg daily recommended for long-term prevention to minimize GI toxicity 1

OR

Clopidogrel 75 mg daily (Level of Evidence: B) 1

• Safe and effective alternative to aspirin
• Superior to aspirin in PAD patients (24% relative risk reduction in CAPRIE trial) 2
• Particularly beneficial in diabetic patients, especially those requiring insulin 3
• Preferred in patients with aspirin intolerance, allergy, or prior vascular event on aspirin 1

Enhanced Antiplatelet Regimens for High-Risk Scenarios

Dual Antiplatelet Therapy (DAPT) Indications

After lower extremity revascularization (Class I Recommendation):

• Low-dose rivaroxaban 2.5 mg twice daily PLUS aspirin 81 mg daily is recommended to reduce major adverse cardiovascular events (MACE) and major adverse limb events (MALE) 1
• After endovascular revascularization: DAPT with P2Y12 antagonist plus aspirin is reasonable for 1-6 months 1
• After surgical revascularization with prosthetic graft: DAPT may be reasonable for at least 1 month 1

Symptomatic PAD with high cardiovascular risk (Class IIb):

• Aspirin plus clopidogrel may be considered in patients not at increased bleeding risk and at high perceived cardiovascular risk 1

Acute coronary syndromes without ST-elevation:

• Aspirin plus clopidogrel reduces cardiovascular death, non-fatal MI, or stroke by 20% compared to aspirin alone over 12 months 1

Post-PCI with Stenting

For ACS patients undergoing PCI:

• Loading dose: aspirin 160-325 mg PLUS ticagrelor 180 mg or prasugrel 60 mg (preferred over clopidogrel 600 mg) 4
• Maintenance: ticagrelor 90 mg twice daily (preferred) or clopidogrel 75 mg daily, plus aspirin 75-100 mg daily for minimum 12 months 4

For elective PCI with drug-eluting stent:

• Aspirin 75-325 mg daily plus clopidogrel 75 mg daily for 3-6 months minimum 4

Critical Contraindications and Exceptions

Do not prescribe antiplatelet therapy if: 1

• Active pathological bleeding 5
• Allergy or intolerance to both aspirin and clopidogrel
• High bleeding risk outweighing cardiovascular benefit
• Patient already on therapeutic anticoagulation (warfarin) without additional indication for antiplatelet therapy 1

Important caveat: Warfarin addition to antiplatelet therapy in PAD patients is of no benefit and potentially harmful due to increased major bleeding risk (Level of Evidence: B) 1

Special Population Considerations

Diabetic patients with established atherosclerotic disease:

• Clopidogrel provides superior cardiovascular risk reduction compared to aspirin alone, particularly in insulin-requiring diabetics 3
• Minimum 12 months DAPT after drug-eluting stent placement unless bleeding risk outweighs benefit 3

Patients requiring anticoagulation plus antiplatelet therapy:

• After revascularization in patients requiring full-intensity anticoagulation for another indication and not at high bleeding risk, adding single antiplatelet therapy is reasonable 1