When to Use Dual Antiplatelet Therapy (Aspirin + Clopidogrel)
Patients should be on aspirin and clopidogrel (dual antiplatelet therapy, DAPT) primarily after acute coronary syndromes and following coronary stent placement, with duration determined by clinical presentation, stent type, and bleeding risk.
Primary Indications for DAPT
Acute Coronary Syndromes (ACS)
For NSTE-ACS (unstable angina/NSTEMI): Initiate aspirin 150-300 mg loading dose (or 75-250 mg IV) plus clopidogrel 300-600 mg loading dose, followed by aspirin 75-100 mg daily plus clopidogrel 75 mg daily for at least 12 months 1, 2.
For STEMI: Administer aspirin plus clopidogrel 75 mg daily (without loading dose if given within hours of symptom onset) for at least 12 months 1, 2.
Note: Prasugrel or ticagrelor are preferred over clopidogrel in ACS patients undergoing PCI, but clopidogrel remains indicated when these agents are unavailable, not tolerated, or contraindicated 1.
After Percutaneous Coronary Intervention (PCI)
For Stable Ischemic Heart Disease (Chronic Coronary Syndrome):
Drug-eluting stents (DES): Aspirin 75-100 mg plus clopidogrel 75 mg daily for 6 months as the default strategy 1.
High bleeding risk patients: Consider shortening DAPT to 1-3 months, then continue single antiplatelet therapy 1.
High ischemic risk patients (complex left main, bifurcation stenting, prior stent thrombosis): May extend DAPT up to 12 months or consider prasugrel/ticagrelor for the first 1-3 months 1.
For ACS with PCI:
Minimum 12 months of DAPT with aspirin plus clopidogrel (or prasugrel/ticagrelor) 1.
In patients without high bleeding risk and no significant bleeding on DAPT, extending beyond 12 months may be reasonable 1.
Secondary Prevention (Without Recent Stenting)
Established Cardiovascular Disease
Recent MI or stroke (without stenting): Clopidogrel 75 mg daily alone is indicated, not in combination with aspirin for long-term secondary prevention 2.
Stable coronary artery disease or peripheral arterial disease: Clopidogrel monotherapy is preferred over DAPT for chronic management 3.
Important caveat: The CHARISMA trial showed that adding clopidogrel to aspirin in stable patients with multiple risk factors (but no established disease) provided no benefit and potentially increased cardiovascular mortality 3.
Special Populations Requiring DAPT
Patients with Atrial Fibrillation Requiring Anticoagulation
After PCI in patients needing oral anticoagulation:
Initial triple therapy: Aspirin (≤100 mg) + clopidogrel 75 mg + oral anticoagulant (preferably DOAC) for ≤1 week after uncomplicated PCI 1.
Then dual therapy: Clopidogrel 75 mg + oral anticoagulant for up to 6 months (standard risk) or up to 12 months (high ischemic risk) 1.
Then monotherapy: Oral anticoagulant alone indefinitely 1.
Triple therapy should ideally not exceed 30 days and is reserved only for highest thrombotic risk patients 1.
After Coronary Artery Bypass Grafting (CABG)
Aspirin monotherapy is recommended post-operatively once bleeding concerns resolve 1.
DAPT may be considered in selected patients at high risk of graft occlusion and low bleeding risk 1.
Duration Algorithms
Bleeding Risk Stratification
Shorten DAPT duration (1-3 months) if:
- Prior intracranial hemorrhage or ischemic stroke 1
- Recent GI bleeding or anemia from GI blood loss 1
- Liver failure, bleeding diathesis, or coagulopathy 1
- Extreme frailty or renal failure requiring dialysis 1
Extend DAPT duration (>12 months) if:
- High ischemic risk: complex multivessel disease, left main stenting, chronic kidney disease, diabetes, prior MI, or multivessel PCI 1
- AND no increased major bleeding risk 1
Critical Safety Considerations
Proton Pump Inhibitor Co-prescription
Mandatory for patients on DAPT at increased GI bleeding risk (history of ulcer, advanced age, concurrent anticoagulation) 1.
Avoid omeprazole and esomeprazole specifically with clopidogrel as they significantly reduce its antiplatelet activity via CYP2C19 inhibition 2.
CYP2C19 Poor Metabolizers
Clopidogrel forms less active metabolite in patients homozygous for nonfunctional CYP2C19 alleles 2.
Consider alternative P2Y12 inhibitor (prasugrel or ticagrelor) in identified poor metabolizers 2.
Discontinuation Risks
Never abruptly stop DAPT after stenting without cardiology consultation—premature cessation dramatically increases risk of stent thrombosis, MI, and death 2, 4.
If surgery is required, continue aspirin and hold only clopidogrel when absolutely necessary, resuming within 5 days post-procedure for drug-eluting stents 1, 4.
Aspirin Dosing
- Maintenance dose should be 75-100 mg daily—higher doses increase bleeding without improving efficacy 1.