Indications for Aspirin and Clopidogrel Loading in Acute Coronary Syndrome
In patients with acute coronary syndrome (ACS), an initial oral loading dose of aspirin (162-325 mg) followed by daily low-dose aspirin, along with a loading dose of a P2Y12 inhibitor such as clopidogrel (300-600 mg), is recommended to reduce death and major adverse cardiovascular events. 1
Aspirin Loading Indications
- Aspirin loading (162-325 mg) should be administered to all patients with ACS without absolute contraindications as soon as possible on presentation, regardless of final management strategy (invasive or non-invasive) 1
- Non-enteric coated aspirin should be chewed when possible to achieve faster onset of antiplatelet action 1
- Loading dose should be administered even for patients already on aspirin therapy 1
- Following loading, maintenance therapy with low-dose aspirin (75-100 mg daily) is recommended for long-term use 1
- For patients unable to take oral medication, rectal or intravenous administration (where available) are alternative options 1
Clopidogrel Loading Indications
- Clopidogrel loading (300 or 600 mg) is indicated in the following ACS scenarios:
- Patients with non-ST-segment elevation ACS (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) without fibrinolytic therapy 1
- Patients unable to take aspirin 1
- Patients in whom a non-interventional approach is planned 1
- Patients in whom catheterization and PCI is planned 1
- For STEMI with fibrinolytic therapy, a reduced loading dose of 300 mg is indicated for patients ≤75 years old, while patients >75 years should start with 75 mg 1
Timing Considerations
- Antiplatelet loading should be initiated as early as possible in the course of ACS 1
- For patients with NSTE-ACS planned for an invasive strategy with timing of angiography anticipated to be >24 hours, upstream treatment with clopidogrel or ticagrelor may be considered to reduce major adverse cardiovascular events 1
- With a 300 mg loading dose of clopidogrel, antiplatelet effects appear within 90 minutes, and after 6 hours, the antithrombotic effects are equivalent to those achieved after 10 days of therapy 1
- The benefits of clopidogrel emerge within 24 hours of initiation of treatment and continue throughout the ensuing 12 months 1
Alternative P2Y12 Inhibitors
- In patients with STEMI managed with primary PCI, prasugrel or ticagrelor should be administered in preference to clopidogrel to reduce major adverse cardiovascular events and stent thrombosis 1
- For prasugrel, a loading dose of 60 mg is indicated for NSTE-ACS or STEMI without fibrinolytic therapy in patients undergoing PCI 1
- For ticagrelor, a loading dose of 180 mg is indicated for NSTE-ACS or STEMI without fibrinolytic therapy 1
- Pretreatment with a loading dose of ticagrelor appears superior in reducing the incidence of PCI-related periprocedural myocardial infarction compared to clopidogrel in Asian patients with ACS 2
Special Considerations and Precautions
- Clopidogrel should be withheld for at least 5 days before elective coronary artery bypass graft surgery 1
- For patients on P2Y12 inhibitors who need non-emergent cardiac surgery, postponing surgery is recommended for at least 3 days after discontinuation of ticagrelor, at least 5 days after clopidogrel, and at least 7 days after prasugrel 1
- The effectiveness of clopidogrel depends on conversion to an active metabolite by the cytochrome P450 system, principally CYP2C19 3
- Consider using another P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers 3
- Avoid concomitant use of clopidogrel with omeprazole or esomeprazole as they significantly reduce the antiplatelet activity of clopidogrel 3
- For patients at high bleeding risk, consider using proton pump inhibitors in combination with dual antiplatelet therapy to reduce bleeding risk 4
Dosing Summary for ACS
- Aspirin: Loading dose 162-325 mg orally, followed by maintenance dose 75-100 mg orally daily 1
- Clopidogrel: