A 68-year-old man with a 3-year history of atrial fibrillation (AF) on warfarin (INR 2.5) presents to the emergency department with acute onset chest pain and dyspnea. ECG shows ST elevation in leads II, III, and aVF. Troponin I is elevated at 2.8 ng/mL. He is diagnosed with acute inferior wall MI. The cardiologist plans urgent percutaneous coronary intervention (PCI). Which of the following is the most appropriate immediate antiplatelet strategy?

Explanation

## Clinical Context This patient has acute STEMI complicating chronic AF on anticoagulation. The standard of care mandates dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) for acute coronary syndrome, regardless of baseline anticoagulation status. ## Rationale for Correct Answer **Key Point:** DAPT is non-negotiable in acute STEMI and takes precedence over bleeding risk concerns. The combination of warfarin + DAPT is standard in AF patients undergoing PCI for ACS. 1. **Aspirin 300 mg loading dose** — immediate antiplatelet effect via COX inhibition 2. **Clopidogrel 600 mg loading dose** — rapid P2Y12 antagonism; preferred in this setting because prasugrel is contraindicated in patients >75 years (this patient is 68, so prasugrel is technically eligible, but clopidogrel is safer given age and bleeding risk) 3. **Continue warfarin** — do NOT discontinue; the INR is therapeutic and AF requires ongoing anticoagulation 4. **Add proton pump inhibitor (PPI)** — gastroprotection for triple therapy (warfarin + aspirin + clopidogrel) **High-Yield:** In AF + ACS, triple therapy (warfarin + aspirin + P2Y12 inhibitor) is the evidence-based approach. The bleeding risk is real but is outweighed by the thrombotic risk of untreated STEMI and AF. ## Duration of Triple Therapy - **Aspirin:** lifelong (post-MI) - **Clopidogrel:** 12 months (standard post-MI duration) - **Warfarin:** lifelong (AF indication) - **PPI:** duration of triple therapy (typically 12 months) ## Comparison of P2Y12 Inhibitors in This Setting | Feature | Clopidogrel | Prasugrel | Ticagrelor | | --- | --- | --- | --- | | Loading dose | 600 mg | 60 mg | 180 mg | | Onset | 2–4 hours | 30 min | 30 min | | Age >75 years | Safe | Avoid | Safe | | Bleeding risk | Moderate | High | High | | CYP3A4 interaction | Yes | No | Yes | | **Preferred in AF + ACS** | **Yes** | **No** | **No** | **Clinical Pearl:** Prasugrel is contraindicated in patients ≥75 years or <60 kg due to increased bleeding risk. Ticagrelor has more drug interactions and higher bleeding rates in elderly patients. Clopidogrel is the safest choice in this 68-year-old with AF on warfarin. ## Why PPI? **Mnemonic: GUT-SAFE** — Gastroprotection Urgent in Triple therapy; Aspirin + anticoagulant = ulcer risk; Famotidine or omeprazole Essential. Triple therapy significantly increases GI bleeding risk (NNH ~50 for major bleed over 12 months). A PPI reduces this by ~70%. ## Bleeding Risk Mitigation - Use clopidogrel (lowest bleeding risk among P2Y12 inhibitors) - Add PPI - Target INR 2–2.5 (lower end of therapeutic range) - Patient education on bleeding signs - Regular INR monitoring [cite:Harrison 21e Ch 297]