A 58-year-old man with diabetes and hypertension presents to the emergency department with acute anterior wall ST-elevation myocardial infarction (STEMI) of 2 hours duration. He is hemodynamically stable with no contraindications to fibrinolysis. The hospital does not have PCI capability and transfer to a PCI-capable centre will take 90 minutes. What is the drug of choice for immediate reperfusion therapy?

## First-Line Fibrinolytic in STEMI **Key Point:** Tenecteplase is the preferred fibrinolytic agent for STEMI when primary PCI is not available within 120 minutes of symptom onset. ### Why Tenecteplase? 1. **Superior fibrin specificity** — Tenecteplase has greater fibrin selectivity compared to other thrombolytics, resulting in less systemic fibrinogenolysis and reduced bleeding risk. 2. **Single bolus administration** — Can be given as a weight-based IV bolus over 5–10 seconds, improving ease and speed of administration in the acute setting. 3. **Faster reperfusion** — Achieves TIMI 3 flow more rapidly than alteplase or streptokinase. 4. **Lower intracranial hemorrhage (ICH) risk** — Meta-analyses show tenecteplase has a lower ICH rate compared to alteplase, particularly in elderly patients. ### Comparative Profile | Agent | Fibrin Specificity | Route | Dosing | ICH Risk | NSTEMI Use | | --- | --- | --- | --- | --- | --- | | **Tenecteplase** | High | IV bolus | Weight-based, single dose | Lowest | Yes | | Alteplase | Intermediate | IV infusion | Weight-based, 90 min protocol | Moderate | Yes | | Streptokinase | Low | IV infusion | Fixed dose, 60 min | Moderate–high | No | | Urokinase | Low | IV infusion | Weight-based | Moderate–high | Rarely used | **High-Yield:** Tenecteplase is now preferred over alteplase in most international guidelines (ESC, ACC/AHA) for STEMI fibrinolysis due to superior safety and efficacy profile. ### Clinical Context **Clinical Pearl:** In this scenario, the patient is within the 2-hour window and PCI is delayed >90 minutes. Fibrinolysis is indicated, and tenecteplase is the agent of choice. Dosing is 30–50 mg IV bolus based on weight (<60 kg: 30 mg; 60–70 kg: 35 mg; 70–80 kg: 40 mg; 80–90 kg: 45 mg; >90 kg: 50 mg). **Warning:** Do not delay fibrinolysis waiting for transfer if PCI-capable centre is >120 minutes away. "Time is muscle" — every 30-minute delay in reperfusion increases 1-year mortality by ~7.5%. [cite:Harrison 21e Ch 297]