Why Fibrin-Specific Thrombolytics Are Preferred Over Non-Specific Agents in STEMI
Fibrin-specific thrombolytic agents (tenecteplase, alteplase, reteplase) should be used instead of non-specific agents (streptokinase) for STEMI because they reduce mortality by approximately 10 additional deaths per 1,000 patients treated and achieve superior coronary artery patency rates. 1, 2
Mortality Benefit
The most compelling reason to choose fibrin-specific agents is their survival advantage:
- Streptokinase increases mortality risk by 14% compared to accelerated alteplase (RR 1.14,95% CI 1.05-1.24), translating to approximately 10 additional deaths per 1,000 patients treated. 3
- Both the 2017 ESC and 2013 ACC/AHA guidelines explicitly recommend fibrin-specific agents as the preferred class when fibrinolysis is indicated. 1, 2
- This mortality difference persists even when modern adjunctive therapy (aspirin, clopidogrel, enoxaparin) is used with both agent types. 4
Superior Coronary Patency
Fibrin-specific agents achieve significantly better restoration of blood flow:
- TIMI 3 flow rates at 90 minutes: tenecteplase 85%, reteplase 84%, alteplase 73-84%, versus streptokinase only 60-68%. 1
- In head-to-head comparison, alteplase achieved TIMI 3 flow in 75% of patients versus only 38% with streptokinase (p < 0.0001). 4
- ST-segment resolution at 60 minutes is significantly faster with alteplase: only 32% of alteplase patients showed absent ST resolution (<30%) compared to 64% of streptokinase patients (p < 0.0001). 4
Bleeding Safety Profile
Contrary to older assumptions, fibrin-specific agents do not carry excess bleeding risk when used appropriately:
- Tenecteplase demonstrates a trend toward lower major bleeding compared to other fibrinolytic regimens (RR 0.79,95% CI 0.63-1.00). 3
- The ASSENT-2 trial comparing tenecteplase and alteplase showed comparable bleeding rates between fibrin-specific agents. 1
- Major bleeding risk is primarily driven by inappropriate addition of glycoprotein IIb/IIIa inhibitors (which increases bleeding 1.27-8.82 times) rather than the choice of fibrinolytic agent itself. 3
Practical Administration Advantages
Fibrin-specific agents offer logistical benefits that reduce time to treatment:
- Tenecteplase: single weight-based bolus (30-50 mg depending on body weight), easiest to administer. 1
- Reteplase: double bolus 30 minutes apart, no weight adjustment needed. 1
- Alteplase: 90-minute infusion requiring weight-based dosing. 1
- Streptokinase: 30-60 minute infusion, but cannot be re-administered due to persistent antibodies lasting ≥10 years. 2
Critical Pitfall: Streptokinase Re-exposure
Never re-administer streptokinase to any patient who has received it previously—antibodies persist for at least 10 years and cause allergic reactions plus treatment failure. 2 If re-occlusion occurs after streptokinase, you must switch to a non-immunogenic fibrin-specific agent or proceed directly to rescue PCI. 2
When Streptokinase Remains Acceptable
Streptokinase is a reasonable alternative only when cost or availability absolutely limits access to fibrin-specific agents, but clinicians must accept the 14% relative increase in mortality risk. 2, 3 The 2017 ESC guidelines frame this as a resource-limited compromise rather than an equivalent choice. 2
Dosing Algorithm for Fibrin-Specific Agents
| Agent | Dose | Administration |
|---|---|---|
| Tenecteplase (preferred) | <60 kg: 30 mg 60-69 kg: 35 mg 70-79 kg: 40 mg 80-89 kg: 45 mg ≥90 kg: 50 mg Age ≥75 years: reduce dose by 50% |
Single IV bolus [1,5] |
| Reteplase | 10 units × 2 doses | Two IV boluses 30 minutes apart [1] |
| Alteplase | 15 mg bolus, then 0.75 mg/kg over 30 min (max 50 mg), then 0.5 mg/kg over 60 min (max 35 mg) | 90-minute infusion [1] |
Adjunctive Therapy Requirements
All fibrinolytic agents require identical adjunctive therapy to maximize efficacy and safety:
- Aspirin 150-325 mg immediately (oral or IV if unable to swallow). 2, 6
- Clopidogrel: 300 mg loading for age <75 years; 75 mg loading for age ≥75 years, then 75 mg daily for ≥14 days. 1, 2
- Anticoagulation: enoxaparin (preferred) or unfractionated heparin until revascularization or up to 8 days. 2, 5
Post-Fibrinolysis Management
Regardless of which fibrin-specific agent is used, all patients require:
- Immediate transfer to PCI-capable center after fibrinolysis administration. 5, 6
- ST-segment assessment at 60-90 minutes: <50% resolution indicates failed reperfusion requiring immediate rescue PCI. 2, 6
- Routine angiography within 2-24 hours after successful fibrinolysis. 5, 6
- Emergency angiography immediately if heart failure, cardiogenic shock, or recurrent ischemia develops. 5, 6
The evidence overwhelmingly supports fibrin-specific agents as the standard of care for fibrinolytic therapy in STEMI, with streptokinase relegated to a resource-limited fallback option only. 1, 2, 3