Clopidogrel and Aspirin Combination Therapy for Chronic Coronary Syndrome
For patients with chronic coronary syndrome (CCS), dual antiplatelet therapy (DAPT) with aspirin 75-100 mg and clopidogrel 75 mg daily is recommended for up to 6 months following percutaneous coronary intervention (PCI), followed by lifelong single antiplatelet therapy. 1
Standard Dosing Regimen
- Aspirin: 75-100 mg once daily 1
- Clopidogrel: 75 mg once daily 1, 2
- For patients requiring immediate antiplatelet effect, clopidogrel can be initiated with a 300 mg loading dose 2
Duration of Therapy Based on Clinical Scenario
After PCI in CCS Patients Without Indication for Oral Anticoagulation:
- Default strategy: DAPT with aspirin 75-100 mg and clopidogrel 75 mg daily for up to 6 months 1
- For patients at high bleeding risk but not high ischemic risk: Discontinue DAPT after 1-3 months and continue single antiplatelet therapy 1
- For patients who are neither at high bleeding risk nor high ischemic risk: Consider stopping DAPT after 1-3 months 1
- For patients with very high risk of life-threatening bleeding: Consider clopidogrel monotherapy for just 1 month 1
Long-term Antiplatelet Therapy After Initial DAPT Period:
- For patients with prior MI or remote PCI: Aspirin 75-100 mg daily is recommended lifelong after the initial DAPT period 1
- Clopidogrel 75 mg daily is a safe and effective alternative to aspirin monotherapy 1
- Recent evidence suggests clopidogrel monotherapy may be superior to aspirin monotherapy in high-risk patients, with significant reduction in death, MI, and stroke without increased bleeding risk 3
After CABG:
- Aspirin 75-100 mg daily is recommended lifelong 1
For CCS Without Prior MI or Revascularization:
- If significant obstructive CAD is present on imaging: Aspirin 75-100 mg daily is recommended lifelong 1
Special Considerations
For Patients with Enhanced Ischemic Risk:
- Adding a second antithrombotic agent to aspirin for extended long-term secondary prevention should be considered in patients with enhanced ischemic risk without high bleeding risk 1
- Options include clopidogrel 75 mg daily, which has been shown to reduce myocardial infarction and ischemic stroke when combined with aspirin, though with increased bleeding risk 4
For Patients with Indication for Oral Anticoagulation:
- After uncomplicated PCI: Early cessation of aspirin (≤1 week) followed by dual therapy with OAC and clopidogrel for up to 6 months (or up to 12 months if high ischemic risk), then OAC alone 1, 5
- DOAC is preferred over VKA when eligible 1, 5
- Ticagrelor or prasugrel is generally not recommended as part of triple antithrombotic therapy 1
Bleeding Risk Management
- A proton pump inhibitor is recommended for patients at increased risk of gastrointestinal bleeding during combination antithrombotic therapy 1
- Note that omeprazole and esomeprazole inhibit CYP2C19 and reduce exposure to clopidogrel's active metabolite, though definitive effects on ischemic events have not been demonstrated 1
Efficacy and Safety Considerations
- Dual therapy with aspirin and clopidogrel reduces major cardiovascular events in high-risk patients but increases bleeding risk 6, 4
- For every 1000 patients treated with combination therapy for 12 months, approximately 13 myocardial infarctions and 23 ischemic strokes are prevented, but 9 major bleeds and 33 minor bleeds are caused 4
- Clopidogrel monotherapy has shown superior efficacy to aspirin monotherapy in recent trials, with significant reduction in death, MI, and stroke without increased bleeding 3