• Fibrinolytic therapy is recommended for the treatment of ST-elevation myocardial infarction (STEMI) and remains a suitable alternative reperfusion strategy for those unable to undergo timely primary percutaneous coronary intervention (PPCI).
• Administration of fibrinolytics is given a Class I recommendation for STEMI reperfusion if given within 12 hours of symptom onset and if angiography cannot be achieved in 2 hours or less.
• 64% of B.C. citizens age ≥ 40 years reside within 120 minutes of a PCI-capable centre. The national average is 80%.
• Fibrinolytic therapy has its greatest benefit the earlier it is administered; up to 30% of STEMIs can be successfully aborted if fibrinolytics are given within the first hour of symptom onset.

• If PPCI is not accessible within 120 min of first medical contact (FMC), fibrinolysis should be considered. Quality processes should target a FMC-to-needle time ≤ 30 min. FMC can either be in the field with a first responder (e.g. paramedic) or after patient presentation to a hospital emergency department (ED).
• Among the available options, fibrin-specific fibrinolytics such as tenecteplase (TNK) or accelerated infusion alteplase (tPA) are preferred.
• Recommended dosing schedules for the various fibrinolytic agents:

*If the patient is older than 75 years, consider using half-dose fibrinolytics to mitigate bleeding risk.

• Following fibrinolytic therapy, rapid transfer to a PCI-capable centre is recommended. Patients will receive:
  • Immediate PCI for those who failed reperfusion on ECG (failure to achieve > 50% ST-segment resolution in the ECG lead with maximal ST elevation, and/or persistent chest pain/hemodynamic/electrical instability). Ideally 60-90 min post-fibrinolysis.
  • Urgent angiography with or without PCI within 24 hours for those with successful fibrinolysis.
•  Facilitated PCI (the administration of adjuvant fibrinolytics with or without glycoprotein (GP) IIb/IIIa inhibitors while in transit for PPCI) is not recommended when access to PPCI is available within 120 min of FMC.

Aspirin (ASA)

• Loading dose: 162 – 325 mg. If vomiting, administer rectally.
• Duration: 81 mg daily continued indefinitely.

Clopidogrel

• Loading dose: 300 mg PO if patient ≤ 75 years old, 75 mg PO if patient > 75 years old.
• Duration: 75 mg PO daily continued for at least 14 days and up to one year.

Unfractionated heparin (UFH) OR Enoxaparin

UFH

• IV bolus of 60 U/kg (maximum 4000 U) followed by an infusion of 12 U/kg (maximum 1000 U) per hour, adjusted to obtain an aPTT of 1.5 to 2.0 times control.
• Duration: 48 hours or until revascularization.

Enoxaparin

• If age < 75 years: 30 mg INTRAVENOUS bolus, followed in 15 min by 1mg/kg subcutaneously every 12 hours (maximum 100 mg for the first 2 doses).
• If age 75 years: no IV bolus, 0.75 mg/kg subcutaneously every 12 hours (maximum 75 mg for the first 2 doses).
• Regardless of age, if CrCl < 30 mL/min: 1 mg/kg subcutaneously every 24 hours.
• Duration: for index hospitalization, up to 8 days or until revascularization.

Other routine adjunctive therapies may be added after reperfusion, if no contraindications. These include oral beta blockers, statins, and ACE inhibitors.

GP IIb/IIIa inhibitors are discouraged as adjunctive therapies to fibrinolytic therapy because the associated risk of major bleeding outweighs any possible mortality benefit.

• The decision to administer fibrinolytic therapy must weigh the likelihood of potential benefit to that of potential harm and be discussed with the patient prior to use.
• In combination with ASA, fibrin-specific fibrinolytics reduce all-cause mortality by up to 6%.
  • Accelerated infusion tPA has an additional reduction in 30-day mortality of 1% when compared to streptokinase. TNK has demonstrated similar mortality benefits as accelerated infusion tPA.
• The baseline risk of intracranial hemorrhage is 0.4% (NNH = 250) and the risk of major non-cerebral bleeds is ~0.7-0.8% (NNH = 137) even without contraindications, and higher if relative contraindications are present.
• Patient factors that may influence the balance of benefit and harm:
  • Increased likelihood of benefit: onset of symptoms < 3 hours, significant ischemic territory at risk (anterior or large inferoposterior/right ventricular MI). Overall mortality benefit for large STEMIs is up to 6%.
  • Decreased likelihood of benefit: onset of symptoms > 6 hours, smaller ischemic territory at risk (uncomplicated inferior or lateral MI). Small infarcts in younger patients (under 75 years of age) may only gain 1-2% mortality advantage.
  • Increased likelihood of major bleeding: age > 75 years, weight < 67 kg, uncontrolled hypertension, renal dysfunction, any other relative contraindication.

1. Wong GC, Welsford M, Ainsworth C, et al. 2019 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Guidelines on the Acute Management of ST-Elevation Myocardial Infarction: Focused Update on Regionalization and Reperfusion. Can J Cardiol. 2019;35(2):107-132

   
   

2. Promes S, Glauser J, Smith M, Torbati S, Brown M. Clinical Policy: Emergency Department Management of Patients Needing Reperfusion Therapy for Acute ST-Segment Elevation Myocardial Infarction. Ann Emerg Med. 2017;70(5):724-739

   
   

3. O’Gara P, Kushner F, Ascheim D, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;127(4):362-425.

   
   

4. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet. 1994;343(8893):311-322.