A 62-year-old man with acute coronary syndrome (NSTEMI) presents to the emergency department 2 hours after symptom onset. He has no contraindications to antiplatelet therapy. Which of the following is the drug of choice for dual antiplatelet therapy in this setting?

Explanation

## Dual Antiplatelet Therapy in Acute Coronary Syndrome **Key Point:** In NSTEMI, the combination of aspirin + a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) is standard. Among these, ticagrelor is preferred in acute coronary syndromes due to superior outcomes in the PLATO trial. ### Why Ticagrelor is First-Line in ACS Ticagrelor is a reversible, direct-acting P2Y12 inhibitor with several advantages: 1. **Faster onset**: Achieves peak platelet inhibition within 2–4 hours (vs. 3–5 days for clopidogrel) 2. **Superior efficacy**: PLATO trial (2009) demonstrated reduced cardiovascular death, MI, and stent thrombosis compared to clopidogrel in ACS 3. **Reversible binding**: Allows faster recovery of platelet function if urgent surgery is needed 4. **No prodrug activation required**: Unlike clopidogrel, ticagrelor is active immediately ### Comparison of P2Y12 Inhibitors | Feature | Clopidogrel | Ticagrelor | Prasugrel | |---------|-------------|-----------|----------| | **Onset** | 3–5 days | 2–4 hours | 30 min–1 hour | | **Binding** | Irreversible | Reversible | Irreversible | | **Prodrug** | Yes | No | Yes | | **ACS superiority** | No | Yes (PLATO) | Yes (TRITON-TIMI 38) | | **Bleeding risk** | Moderate | Moderate | Higher | | **Contraindications** | CYP3A4 inhibitors | Bradycardia, AV block | Age >75 or weight <60 kg | **High-Yield:** Ticagrelor is the preferred P2Y12 inhibitor in acute coronary syndromes (NSTEMI and STEMI) per ESC/AHA guidelines. Prasugrel is also superior to clopidogrel in ACS but carries higher bleeding risk and is contraindicated in elderly/low-weight patients. **Clinical Pearl:** Aspirin is always paired with a P2Y12 inhibitor in ACS; never use P2Y12 inhibitors alone. The combination is maintained for 12 months post-ACS (or longer if stent placed). **Warning:** Clopidogrel is no longer preferred in acute ACS due to slower onset and inferior outcomes compared to ticagrelor/prasugrel, though it remains acceptable if ticagrelor/prasugrel are contraindicated or unavailable.