Acute coronary syndrome (ACS) includes STEMI, NSTEMI, and unstable angina. Antiplatelet therapy is a cornerstone of treatment because platelet activation and aggregation play a central role in coronary thrombus formation.
In most patients with ACS, treatment involves dual antiplatelet therapy (DAPT):
Aspirin + a P2Y12 receptor inhibitor
The commonly used oral P2Y12 inhibitors are clopidogrel, prasugrel, and ticagrelor.
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1. Aspirin
Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), reducing thromboxane A₂ production and platelet aggregation.
Loading Dose
162–325 mg orally
Chewable, non-enteric-coated aspirin is preferred when rapid platelet inhibition is required.
Maintenance Dose
75–100 mg once daily
A commonly used maintenance dose is 81 mg/day.
High-Yield Point
Aspirin should generally be given as early as possible in ACS unless there is a true contraindication, such as significant active bleeding or serious aspirin hypersensitivity.
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2. Clopidogrel
Clopidogrel is an irreversible P2Y12 receptor inhibitor and a prodrug requiring hepatic activation.
Loading Dose
300–600 mg orally
For patients undergoing PCI:
600 mg is generally preferred when rapid platelet inhibition is required.
Maintenance Dose
75 mg once daily
Important Clinical Points
Clopidogrel has slower and more variable platelet inhibition than prasugrel or ticagrelor.
Its effect may vary because activation depends partly on CYP2C19 metabolism.
It remains particularly useful when ticagrelor or prasugrel is contraindicated, unavailable, poorly tolerated, or when clinical circumstances favor clopidogrel.
Fibrinolysis in STEMI
This is an important exam distinction.
Age ≤75 years:
Clopidogrel 300 mg loading dose, followed by 75 mg once daily.
Age >75 years:
Start clopidogrel 75 mg once daily without a loading dose when used with fibrinolytic therapy.
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3. Prasugrel
Prasugrel is an irreversible P2Y12 inhibitor with faster and generally more potent platelet inhibition than clopidogrel.
Loading Dose
60 mg orally
Maintenance Dose
10 mg once daily
For patients with body weight <60 kg:
Consider 5 mg once daily.
Major Contraindication
Previous stroke or transient ischemic attack (TIA)
Prasugrel should not be used in these patients because of increased bleeding risk.
Age ≥75 Years
Prasugrel is generally not recommended routinely in patients ≥75 years because of increased bleeding risk.
If its use is considered appropriate in a selected high-ischemic-risk patient, a lower maintenance dose may be considered.
High-Yield Point
Prasugrel is primarily used in ACS patients undergoing PCI after coronary anatomy is known and PCI is planned.
Avoid routine prasugrel pretreatment before coronary anatomy is established.
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4. Ticagrelor
Ticagrelor is a direct-acting, reversible P2Y12 receptor inhibitor.
Unlike clopidogrel and prasugrel, it does not require metabolic activation to exert its antiplatelet effect.
Loading Dose
180 mg orally
Maintenance Dose
90 mg twice daily
During the first year following ACS, 90 mg twice daily is the standard ACS maintenance regimen when ticagrelor is selected.
Aspirin With Ticagrelor
Use low-dose aspirin maintenance therapy, typically 75–100 mg/day.
Important Adverse Effects
Bleeding
Dyspnea
Bradyarrhythmias or ventricular pauses, particularly early after initiation
Increased uric acid
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Quick Dose Table
Drug| Loading Dose| Maintenance Dose
Aspirin| 162–325 mg| 75–100 mg once daily
Clopidogrel| 300–600 mg| 75 mg once daily
Prasugrel| 60 mg| 10 mg once daily
Ticagrelor| 180 mg| 90 mg twice daily
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Easy Numbers to Remember
Aspirin → 162–325 → 75–100
Clopidogrel → 300/600 → 75
Prasugrel → 60 → 10
Ticagrelor → 180 → 90 BD
These four number combinations cover most oral antiplatelet dosing questions encountered in ACS examinations and routine clinical practice.
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Choosing the P2Y12 Inhibitor
The choice is not based on dose alone.
Important considerations include:
Clinical presentation — STEMI versus NSTE-ACS
PCI versus fibrinolysis versus conservative management
Bleeding risk
Previous stroke or TIA
Age and body weight
Need for oral anticoagulation
Timing of coronary angiography
Previous antiplatelet treatment
Drug availability, adherence, and tolerability
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Pretreatment Before Angiography
One of the important modern ACS concepts is that a P2Y12 loading dose should not automatically be given to every patient before coronary anatomy is known.
In NSTE-ACS patients undergoing an early invasive strategy, routine P2Y12 pretreatment before coronary anatomy is known is generally not recommended.
This approach reduces unnecessary exposure to potent antiplatelet therapy in patients who may subsequently require CABG or have an alternative diagnosis.
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DAPT Duration After ACS
The traditional default strategy following ACS is:
Aspirin + P2Y12 inhibitor for approximately 12 months
However, DAPT duration should now be individualized according to ischemic and bleeding risk.
Selected patients with high bleeding risk may benefit from shorter DAPT or alternative antiplatelet strategies, while patients with high ischemic risk and acceptable bleeding risk may sometimes benefit from more prolonged therapy.
Therefore:
12 months = useful default concept
But not a mandatory duration for every ACS patient.
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Special Situations Worth Remembering
ACS + Fibrinolysis
Clopidogrel is the established oral P2Y12 inhibitor used with fibrinolytic therapy.
Remember the age distinction:
≤75 years → 300 mg loading dose
«75 years → no loading dose; start 75 mg/day»
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Previous Stroke or TIA
Avoid prasugrel.
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Low Body Weight
If prasugrel is used in a patient weighing <60 kg, consider reducing maintenance therapy from 10 mg to 5 mg daily.
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Need for Oral Anticoagulation
Patients with ACS who also require anticoagulation, particularly those with atrial fibrillation undergoing PCI, have substantially increased bleeding risk.
The duration of triple therapy should therefore generally be minimized, followed by an anticoagulant plus a single antiplatelet agent according to the patient's ischemic and bleeding risks.
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Exam Pearls
Aspirin inhibits COX-1 and thromboxane A₂ formation.
Clopidogrel and prasugrel irreversibly inhibit P2Y12 receptors.
Ticagrelor reversibly inhibits P2Y12 receptors.
Ticagrelor does not require metabolic activation.
Prasugrel is contraindicated in previous stroke/TIA.
Prasugrel loading dose = 60 mg.
Ticagrelor loading dose = 180 mg.
Clopidogrel maintenance dose = 75 mg daily.
Ticagrelor maintenance dose in ACS = 90 mg twice daily.
In fibrinolysis, patients >75 years generally receive clopidogrel without a loading dose.
Routine P2Y12 pretreatment before coronary anatomy is known is not recommended for NSTE-ACS patients undergoing an early invasive strategy.
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Take-Home Message
For rapid recall:
Aspirin: 162–325 mg → 75–100 mg OD
Clopidogrel: 300–600 mg → 75 mg OD
Prasugrel: 60 mg → 10 mg OD
Ticagrelor: 180 mg → 90 mg BD
Knowing these doses is important, but safe ACS management also requires choosing the right P2Y12 inhibitor, recognizing contraindications, considering the revascularization strategy, and balancing ischemic benefit against bleeding risk.
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