In a patient older than 70 years with acute ST‑segment elevation myocardial infarction who cannot be transferred to a percutaneous coronary intervention‑capable centre within 120 minutes, what are the recommended thrombolytic agents, dosing adjustments, contraindications, and post‑thrombolysis antithrombotic management?

Thrombolysis in STEMI Patients Above 70 Years

In patients older than 70 years with STEMI who cannot reach a PCI-capable center within 120 minutes, fibrinolytic therapy should be administered immediately with a fibrin-specific agent (tenecteplase, alteplase, or reteplase), followed by mandatory transfer to a PCI center for angiography within 2-24 hours. 1

Age-Specific Considerations

Advanced age is NOT a contraindication to fibrinolytic therapy in STEMI. 1 The guidelines do not specify different eligibility criteria or contraindications based on age alone. However, elderly patients require careful assessment for absolute contraindications, which become more prevalent with advancing age 1:

• Prior intracranial hemorrhage (any time)
• Ischemic stroke within 3 months
• Known intracranial neoplasm, arteriovenous malformation, or aneurysm
• Active bleeding or bleeding diathesis
• Severe uncontrolled hypertension unresponsive to emergency therapy
• Intracranial or intraspinal surgery/trauma within 2 months
• Suspected aortic dissection 1, 2

Recommended Fibrinolytic Agents and Dosing

Use a fibrin-specific agent rather than streptokinase (Class I, Level B recommendation) 1:

Tenecteplase (Preferred for ease of administration)

• Weight-based single bolus dosing 2:
  • <60 kg: 30 mg IV bolus
  • 60-69 kg: 35 mg IV bolus
  • 70-79 kg: 40 mg IV bolus
  • 80-89 kg: 45 mg IV bolus
  • ≥90 kg: 50 mg IV bolus
• Administered as single IV bolus over 5 seconds 2

Alteplase

• 15 mg IV bolus, then 0.75 mg/kg over 30 minutes (maximum 50 mg), then 0.5 mg/kg over 60 minutes (maximum 35 mg) 3
• Total dose should not exceed 100 mg 3

Reteplase

• 10 units IV bolus, followed by second 10 units IV bolus 30 minutes later 1

Fibrin-specific agents achieve superior reperfusion rates (73-85% TIMI 2/3 flow) compared to streptokinase (60-68%) 4, making them the preferred choice when available.

Mandatory Adjunctive Antithrombotic Therapy

Antiplatelet Therapy

All patients receiving fibrinolysis must receive dual antiplatelet therapy 1, 4:

• Aspirin: 162-325 mg loading dose orally or IV immediately (Class I, Level B) 1, 4
• Clopidogrel (NOT prasugrel or ticagrelor initially with fibrinolysis):
  • For patients <75 years: 300 mg loading dose 4
  • For patients ≥75 years: 75 mg loading dose (no loading dose, start with maintenance) 4
  • Continue for minimum 14 days, ideally up to 12 months 4

Critical pitfall: Do NOT use prasugrel or ticagrelor as initial P2Y12 inhibitor with fibrinolysis—these potent agents are reserved for the PCI phase. Clopidogrel is the only recommended P2Y12 inhibitor during fibrinolytic administration 3, 4.

Anticoagulation

Anticoagulation is mandatory until revascularization or up to 8 days of hospitalization (Class I, Level A) 1, 3:

Preferred regimen - Enoxaparin (Class I, Level A) 1, 4:

• For patients <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours
• For patients ≥75 years: NO IV bolus; 0.75 mg/kg subcutaneous every 12 hours (maximum 75 mg for first two doses)
• Adjust for renal impairment (CrCl <30 mL/min): 1 mg/kg subcutaneous every 24 hours

Alternative - Unfractionated heparin (Class I, Level B) 1, 4:

• 60 units/kg IV bolus (maximum 4000 units)
• Initial infusion 12 units/kg/hour (maximum 1000 units/hour)
• Adjust to maintain aPTT 1.5-2.0 times control (50-70 seconds)

Post-Fibrinolysis Management Algorithm

Immediate Transfer (Class I, Level A)

ALL patients receiving fibrinolysis must be transferred immediately to a PCI-capable center regardless of apparent clinical success 1, 3, 4. This is non-negotiable.

Assessment of Fibrinolytic Success

At 60-90 minutes post-fibrinolysis, assess ST-segment resolution 1, 3:

• <50% ST-segment resolution = Failed fibrinolysis → Immediate rescue PCI (Class I, Level A) 1, 3
• ≥50% ST-segment resolution = Successful fibrinolysis → Routine angiography within 2-24 hours (Class I, Level A) 1, 3

Emergency Angiography Indications (Regardless of ST-segment resolution)

Perform emergency angiography and PCI immediately if any of the following develop (Class I, Level A/B) 1, 4:

• Hemodynamic instability or cardiogenic shock
• Electrical instability (ventricular arrhythmias)
• Worsening ischemia or recurrent chest pain
• Heart failure
• Evidence of reocclusion

Routine Angiography Timing

For stable patients with successful fibrinolysis, perform angiography and PCI of the infarct-related artery between 2-24 hours (Class I, Level A) 1, 3. This pharmaco-invasive strategy has been shown non-inferior to primary PCI in patients with transfer delays >60 minutes 5.

Timing Considerations Specific to Elderly Patients

The benefit of fibrinolysis is greatest when administered within 2 hours of symptom onset 1. For patients >70 years presenting very early (<2 hours from symptom onset), the mortality benefit is particularly pronounced if PCI delay exceeds 60 minutes 1.

However, fibrinolysis remains indicated up to 12 hours from symptom onset when PCI cannot be achieved within 120 minutes of first medical contact (Class I, Level A) 1.

Critical Contraindications and Safety Monitoring

Bleeding Risk Management

Elderly patients have inherently higher bleeding risk, particularly intracranial hemorrhage 2. To minimize bleeding complications:

• Avoid intramuscular injections 2
• Minimize nonessential patient handling for first few hours 2
• Avoid internal jugular and subclavian venous punctures 2
• If arterial puncture necessary, use upper extremity vessel accessible to manual compression; apply pressure for ≥30 minutes 2
• Monitor for signs of bleeding during and for several hours after infusion 2

Reperfusion Arrhythmias

Have antiarrhythmic therapy immediately available for bradycardia and ventricular irritability, as coronary thrombolysis commonly causes reperfusion arrhythmias (sinus bradycardia, accelerated idioventricular rhythm, ventricular tachycardia) 2.

Hypersensitivity Reactions

Monitor for allergic reactions (anaphylaxis, angioedema, laryngeal edema, rash, urticaria) during and for several hours after fibrinolytic administration; have antihistamines and corticosteroids available 2.

When Fibrinolysis Should NOT Be Used

Do NOT administer fibrinolysis if 1, 3:

• Primary PCI can be performed within 120 minutes of first medical contact (Class I, Level A)
• Patient presents >48 hours after symptom onset and is asymptomatic (Class III, Level A)
• ECG shows only ST-segment depression (unless true posterior MI suspected)
• Any absolute contraindication present

Evidence Supporting This Approach

The Fibrinolytic Therapy Trialists' collaborative meta-analysis of 58,600 patients demonstrated absolute mortality reductions of 3% for patients presenting within 0-6 hours and 2% for those presenting 7-12 hours from symptom onset 1. Recent real-world data from large STEMI networks show that when transfer delays exceed 140 minutes, fibrinolysis followed by transfer achieves acceptable outcomes, though primary PCI remains superior when achievable within guideline time windows 6. The pharmaco-invasive strategy combining fibrinolysis with routine early angiography has been validated as non-inferior to primary PCI in patients with anticipated transfer delays >60 minutes 5.