Antiplatelet Therapy Regimen
The recommended antiplatelet regimen depends critically on the clinical indication: for acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin 75-100 mg daily plus a P2Y12 inhibitor (ticagrelor or prasugrel preferred over clopidogrel) for 12 months is the standard approach, while for stable coronary artery disease or secondary prevention after MI/stroke, aspirin 75-100 mg daily as monotherapy is recommended. 1
Acute Coronary Syndrome (ACS)
Initial Therapy and Drug Selection
For patients with ACS, DAPT should be initiated immediately with aspirin plus a P2Y12 inhibitor 1:
- Ticagrelor is the preferred P2Y12 inhibitor (180 mg loading dose, then 90 mg twice daily) regardless of initial treatment strategy, including patients pre-treated with clopidogrel 1
- Prasugrel is recommended for P2Y12 inhibitor-naïve patients (60 mg loading dose, then 10 mg daily) undergoing percutaneous coronary intervention (PCI), unless contraindicated 1
- Clopidogrel (300-600 mg loading dose, then 75 mg daily) is reserved for patients who cannot receive ticagrelor or prasugrel, including those with prior intracranial bleeding or requiring oral anticoagulation 1, 2
Critical Contraindications
Prasugrel must not be administered to patients with prior stroke or TIA due to increased risk of cerebrovascular events, and should be avoided in patients ≥75 years or weighing <60 kg 1, 3. Ticagrelor is contraindicated in patients with previous intracranial hemorrhage or ongoing bleeding 1.
Aspirin Dosing
Daily aspirin dose should be 75-100 mg (commonly 81 mg in the US) during DAPT, not higher doses 1. This low-dose regimen minimizes bleeding risk while maintaining efficacy 1.
Duration of DAPT
Standard Duration
For ACS patients treated with PCI and stent placement, DAPT should continue for 12 months unless excessive bleeding risk exists (e.g., PRECISE-DAPT score ≥25) 1:
- Bare-metal stents (BMS): Minimum 1 month of DAPT, ideally 12 months 1
- Drug-eluting stents (DES): Minimum 3-6 months (varies by stent type: 3 months for -limus stents, 6 months for -taxel stents), ideally 12 months 1
Medical Management Without Revascularization
For ACS patients managed medically without revascularization, P2Y12 inhibitor therapy (ticagrelor or clopidogrel) should continue for at least 12 months 1. Prasugrel is not recommended in this population 1.
Extended DAPT Beyond 12 Months
Continuation of DAPT beyond 12 months may be reasonable in patients who have tolerated therapy without bleeding complications and are not at high bleeding risk 1. However, this must be weighed against increased bleeding risk, particularly intracranial hemorrhage 1.
Shortened DAPT Duration
For patients at high bleeding risk, discontinuation of P2Y12 therapy after 6 months may be reasonable following DES implantation, particularly if major bleeding develops or oral anticoagulation is required 1.
STEMI Treated With Fibrinolytic Therapy
Clopidogrel (300 mg loading dose in patients <75 years, then 75 mg daily) should be continued for a minimum of 14 days and ideally 12 months when combined with aspirin in STEMI patients receiving fibrinolysis 1.
Stable Coronary Artery Disease and Secondary Prevention
Monotherapy After Initial Period
After completing the initial DAPT period (typically 12 months), transition to single antiplatelet therapy 1:
- Aspirin 75-100 mg daily is the first-line agent for long-term secondary prevention in coronary artery disease 1, 4
- Clopidogrel 75 mg daily is preferred for patients with cerebrovascular disease or those intolerant to aspirin 2, 4
Recent MI or Stroke Without Acute Intervention
For patients with established peripheral arterial disease or history of MI or stroke, aspirin 75-325 mg daily (or clopidogrel 75 mg daily as alternative) is recommended without a loading dose 1, 2.
Acute Ischemic Stroke/TIA
For minor ischemic stroke or high-risk TIA, DAPT with aspirin 160-325 mg loading dose plus clopidogrel 300-600 mg loading dose, followed by aspirin 81 mg daily plus clopidogrel 75 mg daily for 21 days, then transition to single antiplatelet therapy 5. This must be initiated within 12-24 hours of symptom onset after excluding intracranial hemorrhage on neuroimaging 5.
Combination Antiplatelet and Anticoagulation
For patients with stable coronary artery disease and/or peripheral arterial disease, aspirin plus low-dose rivaroxaban may be considered to prevent major adverse limb and cardiovascular complications 1.
Bleeding Risk Mitigation
Proton Pump Inhibitor Co-Administration
A proton pump inhibitor (PPI) should be prescribed in combination with DAPT to reduce gastrointestinal bleeding risk 1. Pantoprazole or rabeprazole are preferred over omeprazole or esomeprazole due to lower drug-drug interaction potential with clopidogrel 1, 2.
Procedural Considerations
Radial artery access is recommended over femoral access for coronary angiography and PCI when performed by an experienced radial operator 1.
Perioperative Management
Aspirin should be continued perioperatively if bleeding risk allows, and DAPT should not be discontinued within the first month after stent placement for elective non-cardiac surgery 1. When surgery with major bleeding risk is necessary, interrupt P2Y12 inhibitor therapy for 5 days prior to surgery and resume as soon as hemostasis is achieved 1, 2.
Important Caveats
Avoid concomitant use of clopidogrel with omeprazole or esomeprazole as these significantly reduce clopidogrel's antiplatelet activity through CYP2C19 inhibition 2. Consider alternative P2Y12 inhibitors in patients identified as CYP2C19 poor metabolizers, as clopidogrel effectiveness is substantially reduced in this population 2.
Routine platelet function testing to adjust antiplatelet therapy is not recommended before or after elective stenting 1.