A 58-year-old man with hypertension and dyslipidemia presents with chest pain at rest for 2 hours. ECG shows ST-segment depression in leads II, III, aVF with elevated troponin I. He is haemodynamically stable. Which of the following is the drug of choice for immediate antiplatelet therapy in this patient with NSTEMI?

## Dual Antiplatelet Therapy in NSTEMI **Key Point:** In NSTEMI, dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is the cornerstone of acute management. The choice of P2Y12 inhibitor depends on the clinical scenario and PCI strategy. ### P2Y12 Inhibitor Selection in NSTEMI | Drug | Loading Dose | Onset | Advantages | Disadvantages | | --- | --- | --- | --- | --- | | **Clopidogrel** | 600 mg | 2–4 hrs | Older agent, well-studied | Slower onset, prodrug (CYP3A4 dependent) | | **Ticagrelor** | 180 mg | 30–60 min | Faster onset, direct-acting, reversible | Bradycardia, dyspnoea, AV block risk | | **Prasugrel** | 60 mg (5–10 mg/day) | 30 min | Potent, faster than clopidogrel | Bleeding risk, contraindicated in prior stroke | **High-Yield:** Ticagrelor is the **preferred P2Y12 inhibitor** in NSTEMI because: 1. Faster onset of action (30–60 min vs 2–4 hrs for clopidogrel) 2. Direct-acting (not a prodrug) — no CYP3A4 dependence 3. Reversible binding — shorter half-life if urgent surgery needed 4. Superior outcomes in PLATO trial (landmark NSTEMI/UA trial) **Clinical Pearl:** Prasugrel is an alternative in NSTEMI but is **contraindicated in prior stroke/TIA** (bleeding risk) and is less preferred than ticagrelor in routine practice. Clopidogrel is reserved for patients with contraindications to ticagrelor (e.g., bradycardia, AV block, pregnancy) or those already on it. **Warning:** Aspirin monotherapy is **insufficient** in NSTEMI — dual antiplatelet therapy is mandatory to reduce stent thrombosis and recurrent ACS events. ### Mechanism of Action ```mermaid flowchart TD A[NSTEMI Diagnosis]:::outcome --> B[Aspirin + P2Y12 Inhibitor]:::action B --> C{Which P2Y12?}:::decision C -->|Preferred| D[Ticagrelor 180 mg]:::action C -->|Alternative| E[Prasugrel 60 mg]:::action C -->|If contraindication| F[Clopidogrel 600 mg]:::action D --> G[Faster platelet inhibition]:::outcome E --> H[Potent but bleeding risk]:::outcome F --> I[Slower onset]:::outcome ``` [cite:Harrison 21e Ch 297]