A 58-year-old man presents to the emergency department with acute anterior wall STEMI of 2 hours duration. He is haemodynamically stable with no contraindications to fibrinolysis. Primary PCI is not available within 120 minutes. What is the drug of choice for immediate reperfusion therapy?

Explanation

## Fibrinolytic Agent Selection in STEMI **Key Point:** Alteplase (tissue plasminogen activator, tPA) is the preferred fibrinolytic agent for acute STEMI when primary PCI is not available within 120 minutes of symptom onset. ### Mechanism of Action Alteplase is a recombinant tissue plasminogen activator that: 1. Binds to fibrin in the thrombus 2. Converts plasminogen to plasmin 3. Causes selective fibrinolysis of the coronary thrombus 4. Achieves TIMI 3 flow in ~50–60% of cases when given within 12 hours of symptom onset ### Dosing in STEMI - **Weight-based regimen:** 15 mg IV bolus, then 0.75 mg/kg over 30 min (max 50 mg), then 0.5 mg/kg over 60 min (max 35 mg) - Total dose typically 100 mg over 90 minutes ### Comparative Efficacy of Fibrinolytics | Agent | Fibrin Selectivity | TIMI 3 Flow | Intracranial Bleed Risk | Preferred Use | |-------|-------------------|------------|------------------------|---------------| | **Alteplase (tPA)** | High | 50–60% | Moderate (0.7–0.9%) | **First-line** | | Streptokinase | Low | 30–40% | Lower (0.3%) | Cost-effective alternative | | Reteplase | Intermediate | 45–55% | Similar to tPA | Alternative if tPA unavailable | | Tenecteplase | High | 55–65% | Similar to tPA | Single bolus; easier administration | **High-Yield:** Alteplase is superior to streptokinase in reducing 30-day mortality (6.3% vs 7.3%) and is the preferred agent in most high-income settings [cite:Harrison 21e Ch 297]. ### Clinical Pearl **Timing is critical:** Fibrinolysis must be initiated as soon as possible after symptom onset. The "door-to-needle" time should be <30 minutes. The benefit of fibrinolysis decreases significantly after 12 hours of symptom onset. ### Contraindications to Fibrinolysis - Active bleeding or bleeding disorder - Recent intracranial surgery or head trauma - Severe uncontrolled hypertension (>180/110 mmHg) - Ischaemic stroke within 3 months - Aortic dissection **Warning:** Do not confuse fibrinolytic agents with antiplatelet agents (clopidogrel, ticagrelor) or beta-blockers (metoprolol). These are adjunctive therapies, not primary reperfusion agents.