What is the role of thrombolysis in acute myocardial infarction (MI)?

Role of Thrombolysis in Acute Myocardial Infarction

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for STEMI patients when it can be performed in a timely manner (within 90 minutes of first medical contact), but thrombolytic therapy remains a vital treatment option when timely PCI is not available. 1

Indications for Thrombolysis

Thrombolysis should be considered in the following scenarios:

• When primary PCI cannot be performed within 120 minutes of STEMI diagnosis 1
• For patients presenting within 12 hours of symptom onset with ST-segment elevation or new left bundle-branch block 2
• Most beneficial when administered within the first 3 hours after symptom onset 2
• No upper age limit, though risk-benefit assessment is crucial in elderly patients 2

Efficacy and Benefits

Thrombolytic therapy provides significant mortality reduction:

• Approximately 30 early deaths prevented per 1000 patients treated 2
• 20 deaths prevented per 1000 patients treated between 7-12 hours after symptom onset 2
• Greatest absolute benefit seen in high-risk patients 2
• Mortality reduction of nearly 50% when administered within one hour of symptom onset 3

Time-Dependent Efficacy

The benefit of thrombolysis is highly time-dependent:

• Most effective when administered early (within first 3 hours) 2
• Efficacy decreases significantly with time:
  • 51% mortality reduction when given within 1 hour of symptom onset
  • 20% reduction when given between 3-6 hours 2
  • Limited or no benefit beyond 12 hours 2

Thrombolytic Agents

Several thrombolytic agents are available:

• Streptokinase: 250,000-unit bolus, followed by 100,000 units/hour for 24 hours 2
• Tenecteplase (TNKase): Single-bolus weight-adjusted dosing, with similar efficacy to alteplase but with fewer non-cerebral bleeds 4
• Alteplase (rt-PA): 100 mg infused over 2 hours 2
• Reteplase: Double-bolus administration 2

Risks and Complications

Thrombolysis carries important risks:

• Stroke: Approximately 3.9 extra strokes per 1000 patients treated 2
• Intracranial hemorrhage: Risk of approximately 0.5% 2, 4
• Major non-cerebral bleeding: Occurs in 4-13% of patients 2
• Risk factors for bleeding: Advanced age, lower weight, female gender, prior cerebrovascular disease, hypertension 2

Adjunctive Therapies with Thrombolysis

To optimize outcomes with thrombolysis:

• Aspirin: 162-325 mg immediately upon STEMI diagnosis 1, 4
• Anticoagulation: Intravenous heparin adjusted to maintain aPTT at 50-75 seconds for 24-48 hours 2, 4
• Consider early catheterization after successful thrombolysis within 24 hours, even in asymptomatic patients 2

Pharmacoinvasive Strategy

A combined approach may be beneficial:

• Routine immediate or early catheterization followed by stenting after fibrinolytic therapy reduces death (4.4% vs 7.1%) and reinfarction (3.6% vs 6.1%) compared to delayed or ischemia-guided approach 2
• Rescue PCI is recommended if thrombolysis fails within 45-60 minutes after starting administration 2

Contraindications to Consider

Key contraindications to thrombolysis include:

• Prior intracranial hemorrhage
• Known cerebrovascular lesion
• Recent major trauma or surgery
• Active bleeding or bleeding diathesis
• Suspected aortic dissection
• For streptokinase: Previous exposure or known allergy (use alternative agent) 2

Implementation in Practice

For optimal outcomes:

• Door-to-needle time should be within 30 minutes of first medical contact 1
• Pre-hospital thrombolysis can reduce time to treatment and improve outcomes in appropriate settings 2
• Develop clear protocols for rapid diagnosis and treatment decision-making
• Consider the entire system of care when deciding between thrombolysis and primary PCI

Special Considerations

• In cardiogenic shock, primary PCI is strongly preferred over thrombolysis 2
• For patients with contraindications to thrombolysis, immediate transfer for primary PCI is essential 2
• The benefit of thrombolysis appears relatively stable across age groups, though bleeding risk increases with age 2

When primary PCI cannot be delivered within the recommended timeframe, thrombolysis remains a critical reperfusion strategy that can significantly reduce mortality in STEMI patients, especially when administered early after symptom onset.