What is the role of thrombolysis (thrombolytic therapy) in the management of myocardial infarction (MI)?

Thrombolysis in Myocardial Infarction

Thrombolytic therapy reduces mortality by 21% in ST-elevation myocardial infarction when primary PCI cannot be performed within 90-120 minutes of first medical contact, with maximum benefit achieved when administered within the first hour of symptom onset. 1

Primary Reperfusion Strategy Selection

Primary PCI is the preferred reperfusion strategy if it can be performed within 90-120 minutes by skilled operators with access to emergency cardiac surgery. 1, 2 If these conditions cannot be met, thrombolysis should be initiated within 10 minutes of STEMI diagnosis. 2

When to Choose Thrombolysis Over Primary PCI

• Administer thrombolysis when primary PCI cannot be achieved within 90-120 minutes of first medical contact or STEMI diagnosis. 1, 2
• Greatest mortality benefit occurs when thrombolysis is given within the first hour of symptom onset, saving 35 lives per 1000 patients treated, compared to only 16 lives per 1000 when given 7-12 hours after onset. 1
• Definite benefit exists up to 12 hours from symptom onset, though efficacy decreases with time. 1

Eligibility Criteria for Thrombolysis

Indications

• ST-segment elevation ≥1 mV in contiguous leads on 12-lead ECG provides strong evidence of thrombotic coronary occlusion. 1
• New or presumably new left bundle branch block with symptoms consistent with acute MI should be managed identically to ST-elevation. 1

Absolute Contraindications

• Active internal bleeding 3
• History of cerebrovascular accident 3
• Intracranial or intraspinal surgery or trauma within 2 months 3
• Intracranial neoplasm, arteriovenous malformation, or aneurysm 3
• Known bleeding diathesis 3
• Severe uncontrolled hypertension 3

Critical Exclusion

Patients without ST-segment elevation should NOT receive thrombolytic therapy, as it provides no benefit and increases bleeding risk. 1

Mortality Benefit and Time Dependency

• Overall 21% proportional reduction in 35-day mortality, corresponding to 21 deaths prevented per 1000 patients treated. 1
• Time-to-treatment is the most powerful predictor of benefit:
  • 0-1 hour: 35 lives saved per 1000 treated 1
  • 1-6 hours: Substantial benefit 1
  • 7-12 hours: 16 lives saved per 1000 treated 1
• Benefit applies irrespective of age, gender, or comorbidities such as diabetes mellitus, though magnitude varies. 1

Bleeding Risks and Risk Stratification

Intracranial hemorrhage (ICH) is the most serious complication, occurring predominantly within the first 24 hours and proving fatal in 50-67% of cases. 1, 3

Risk Factors for Intracranial Hemorrhage

• Age >65 years (odds ratio 2.2) 1
• Body weight <70 kg (odds ratio 2.1) 1
• Hypertension on presentation (odds ratio 2.0) 1
• Use of tissue plasminogen activator/alteplase (odds ratio 1.6) 1

Risk Stratification

• 0 risk factors: 0.26% ICH risk 1
• 1 risk factor: 0.96% ICH risk 1
• 2 risk factors: 1.32% ICH risk 1
• 3+ risk factors: >1.5% ICH risk (generally considered unacceptably high) 1

Adjust thrombolytic dosing downward for patients weighing <67 kg (alteplase 90-minute regimen) or <65 kg (180-minute regimen) to reduce bleeding risk. 1

Post-Thrombolysis Management: The Pharmaco-Invasive Strategy

Following thrombolysis, all patients should be transferred to a PCI-capable center for routine early angiography within 3-24 hours, even if thrombolysis appears successful. 1

Rescue PCI

• Perform immediate angiography and rescue PCI if ST-segment resolution is <50% at 60-90 minutes, indicating failed thrombolysis. 1
• Do NOT re-administer fibrinolysis for failed thrombolysis, as it has not been shown beneficial. 1

Routine Early PCI After Successful Thrombolysis

• Perform angiography 3-24 hours after successful thrombolysis (defined as >50% ST-segment resolution, reperfusion arrhythmias, or chest pain resolution). 1
• This pharmaco-invasive strategy reduces reinfarction and recurrent ischemia compared to watchful waiting. 1

Critical Pitfall: Facilitated PCI

Do NOT routinely administer full-dose thrombolytics immediately before planned primary PCI (facilitated PCI). 3 The ASSENT-4 trial demonstrated:

• Higher mortality (6.7% vs 4.9%) 3
• Increased cardiogenic shock (6.3% vs 4.8%) 3
• More congestive heart failure (12% vs 9.2%) 3
• Higher recurrent MI rates (6.1% vs 3.7%) 3

In patients with large STEMI, choose EITHER thrombolysis OR primary PCI as the primary reperfusion strategy—not both simultaneously. 3

Adjunctive Therapies with Thrombolysis

Immediate Administration

• Aspirin 160-325 mg orally immediately upon arrival 1, 2
• Unfractionated heparin or enoxaparin as anticoagulation 1, 2
• Clopidogrel 75 mg daily (loading dose followed by maintenance) 2

Avoid

• Do NOT administer aspirin until >24 hours post-thrombolysis if using IV thrombolytic therapy, to minimize bleeding risk. 4
• Prophylactic antiarrhythmic agents are NOT recommended in the first 24 hours. 1

Practical Implementation

Minimize Bleeding Complications

• Avoid intramuscular injections and nonessential patient handling for the first few hours. 3
• Perform arterial and venous punctures carefully and only when required. 3
• Avoid internal jugular and subclavian venous punctures to minimize bleeding from noncompressible sites. 3
• If arterial puncture is necessary, use upper extremity vessels accessible to manual compression and apply pressure for ≥30 minutes. 3

Monitoring

• Have anti-arrhythmic therapy immediately available (atropine, lidocaine, transcutaneous pacing, defibrillator, epinephrine) as reperfusion arrhythmias are common. 1, 3
• Monitor for hypersensitivity reactions during and for several hours after infusion. 3

Common Clinical Pitfalls

• Delaying thrombolysis while arranging transfer for primary PCI when PCI cannot be achieved within 90-120 minutes—every 30-minute delay costs lives. 1
• Administering thrombolytics to patients without ST-elevation or new LBBB—this provides no benefit and increases bleeding risk. 1
• Using facilitated PCI (full-dose thrombolytics before planned immediate PCI)—this increases mortality and should be avoided. 3
• Failing to transfer patients to PCI-capable centers after thrombolysis—the pharmaco-invasive strategy improves outcomes. 1
• Not adjusting thrombolytic doses for low body weight patients—this increases ICH risk unnecessarily. 1