## First-Line Dual Antiplatelet Therapy in ACS **Key Point:** In acute coronary syndrome (both STEMI and NSTEMI), the combination of aspirin + a P2Y₁₂ inhibitor (clopidogrel, ticagrelor, or prasugrel) is standard. Among the P2Y₁₂ inhibitors, ticagrelor and prasugrel are preferred over clopidogrel due to superior outcomes in clinical trials. ### Why Ticagrelor or Prasugrel Over Clopidogrel? | Feature | Clopidogrel | Ticagrelor | Prasugrel | |---------|-----------|-----------|----------| | **Onset of action** | 3–5 days (slow) | 30 min (rapid) | 30 min (rapid) | | **Mechanism** | Prodrug; irreversible P2Y₁₂ inhibitor | Direct-acting; reversible | Prodrug; irreversible | | **PLATO trial (ACS)** | Baseline | Superior to clopidogrel | — | | **TRITON-TIMI 38** | — | — | Superior to clopidogrel | | **Bleeding risk** | Moderate | Moderate–high | Moderate–high | | **Contraindications** | — | Bradycardia, AV block | Age >75 yr, body weight <60 kg | **High-Yield:** Ticagrelor is preferred in acute NSTEMI/STEMI because it achieves platelet inhibition within 30 minutes (vs. 3–5 days for clopidogrel) and has shown superior outcomes in the PLATO trial. Prasugrel is equally effective but carries higher bleeding risk and is contraindicated in elderly patients or those with prior stroke. ### Clinical Pearl **Aspirin + Ticagrelor** is the guideline-recommended first-line DAPT regimen for ACS because: 1. Rapid onset of action (critical in acute MI) 2. Superior reduction in cardiovascular death and MI (PLATO trial) 3. Suitable for most patients without age/weight restrictions 4. Better outcomes than aspirin + clopidogrel in acute settings **Warning:** Do NOT use clopidogrel monotherapy in acute ACS—it is too slow-acting. Clopidogrel is acceptable only in chronic stable CAD or when ticagrelor/prasugrel are contraindicated. [cite:Harrison 21e Ch 297]
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