Introduction
Percutaneous coronary intervention (PCI) is the preferred reperfusion strategy during a cardiac arrest; thrombolytic therapy is an option without PCI capability, followed by transfer to a PCI capable center.
Thrombolytic therapy is most effective when administered within 30 minutes of first medical contact, however, may be considered within 12 – 24 hours of symptom onset and ongoing ischemia or extensive ST elevation. During ACS-Induced Cardiac Arrest, the goal for fibrinolysis is 30 minutes and reperfusion with PCI is preferred, however, if PCI is delayed, fibrinolytics therapy could be considered.
Key Points
- PCI is the preferred reperfusion strategy in cardiac arrest with suspected STEMI; fibrinolytics are an option when PCI is unavailable or delayed.
- Thrombolytic therapy is most effective within 30 minutes of first medical contact, with a 30-minute fibrinolysis goal in ACS-induced cardiac arrest.
- Tenecteplase and alteplase are both appropriate fibrinolytics when PCI is unavailable; tenecteplase has been evaluated as a 30–50 mg bolus.
- When alteplase is the only available agent, data support bolus therapy with or without a weight-based infusion during cardiac arrest.
Clinical Detail
Comparison of the two fibrinolytic agents most often used for STEMI when primary PCI is unavailable.
| Parameter | Alteplase | Tenecteplase |
|---|---|---|
| MOA | Initiates fibrinolysis by binding to fibrin in a thrombus and converts entrapped plasminogen to plasmin | Promotes initiation of fibrinolysis by binding to fibrin and converting plasminogen to plasmin; similar to alteplase but more fibrin specific |
| Dose | Weight based: > 67kg: infuse 15mg IV bolus over 1-2 minute, followed by 50mg infusion over 30 minutes, then 35mg over 1 hour (max total dose 100mg) ≤ 67kg: infuse 15mg IV bolus over 1-2 minutes, followed by 0.75mg/kg infusion over 30 minutes, then 0.5mg/kg over 1 hour (max total dose 100mg) | Weight based: < 60kg: 30mg ≥ 60 to < 70kg: 35mg ≥ 70 to < 80kg: 40mg ≥ 80 to < 90kg: 45mg ≥ 90kg: 50mg |
| Administration | Bolus administered over 1 minute followed by infusion | Single bolus over 5 seconds |
| PK/PD | Duration: 1 hour after infusion terminated Distribution: approximates plasma volume Half-life elimination: 5 minutes Excretion: hepatic and plasma clearance | Distribution: weight related Metabolism: hepatic Half-life elimination: biphasic; initial 20-24 min, terminal 90-130 min Excretion: plasma clearance |
| Adverse Effects | Intracranial hemorrhage Ecchymosis GI/GU hemorrhage Sepsis Cerebrovascular accident | Hemorrhage and hematoma Cerebrovascular accident |
| Drug Interactions and Warnings | Tranexamic acid, avoid combination Internal bleeding, thromboembolic events, cholesterol embolization | Tranexamic acid, avoid combination Internal bleeding, thromboembolic events, arrhythmias |
| Contraindications | Active internal bleeding Ischemic stroke within 3 months except when within 4.5 hours Severe uncontrolled hypertension | Active internal bleeding Severe uncontrolled hypertension Recent intracranial/intraspinal surgery Ischemic stroke within 3 months |
| Compatibility | May be diluted in equal volume with: 0.9% sodium chloride D5W Incompatible with dextrose | — |
Evidence
Overview of Evidence
| Author, year | Design / sample size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Guillermin 2016a | Meta-analysis of RCT (n=18,208) | Tenecteplase 30-50mg vs alteplase 80-100mg | Bleeding 4.8% in tenecteplase vs 5.8% alteplase (p=0.0002) No difference in mortality at 30 days |
| Llevadot 2001 | Retrospective review (38 studies) | Reteplase Anoteplase Tenecteplase | Tenecteplase and reteplase associated with accelerated infusion and more convenient by bolus administration Administration of a less fibrin-specific agent may cause greater systemic coagulopathy with potential for more bleeding |
| Boersma 1996 | Retrospective review (n=50,246) | Fibrinolytic therapy vs placebo | Mortality reduction in patients treated within 2 hours compared to later (p=0.001) |
| GUSTO 1993 | Randomized, controlled trial (n=41,021) | Streptokinase + SQ heparin Streptokinase + IV heparin Alteplase + IV heparin Alteplase + Streptokinase + IV heparin | Alteplase administered over 1.5 hours with IV heparin provide survival over standard therapy Thrombolytic therapy administered within 24-48 hours of admission |
| Armstrong 2013b | Randomized controlled trial (n=1892) | PCI vs bolus tenecteplase, clopidogrel, and enoxaparin | Tenecteplase administration prehospital resulted in effective reperfusion when PCI was not completed within 1 hour Fibrinolytic therapy associated with increase risk of intracranial bleeding |
Cardiac Arrest Data
| Author, year | Design / sample size | Intervention & Comparison | Outcome |
|---|---|---|---|
| Bottiger 2001 | Prospective cohort (n=40) | Alteplase 50 mg bolus, repeat 50 mg in 30 minutes vs placebo | Increase in ROSC (68% vs 44%), ICU admission compared to placebo |
| Schreiber 2002 | Retrospective chart review (n=157) | Alteplase 15mg bolus followed by 50mg infusion over 30 min and 35mg over 60 min | Thrombolytic therapy achieved better functional neurological recovery more frequently (p=0.03) |
| Lederer 2004 | Retrospective chart review (n=108) | Alteplase 100 mg (15 mg followed by 85 mg over 90 min) | 81% of patients who received thrombolytic therapy were discharged without neurological deficit 67% of patients were still alive 5-10 years after the event |
| Li 2006 | Meta-analysis | Alteplase 15mg bolus followed by 50mg infusion over 30 min and 35mg over 60 min | Thrombolytic therapy improved the rate of ROSC (p < 0.01) 48% of patients had acute coronary artery obstruction |
| Bottiger 2008 | Randomized, double-blind, multicenter trial (n=1050) | Tenecteplase 30mg if < 60kg Tenecteplase 35mg if 60-69kg Tenecteplase 40mg if 70-79kg Tenecteplase 45mg if 80-89kg Tenecteplase 50mg if > 90kg Placebo | No difference in tenecteplase and placebo in 30-day survival, ROSC, survival, or neurologic outcomes Increased intracranial hemorrhages in tenecteplase patients |
| Ruiz-Bailen 2001 | Retrospective cohort (n=303) | Streptokinase Alteplase accelerated regimen Alteplase double bolus | Systemic thrombolysis patients had a lower mortality, less mechanical ventilation, fewer CPR attempts (p < 0.0001) No fatal hemorrhagic complications |
a Administered as tenecteplase 30-50mg bolus and alteplase 15mg bolus followed by 0.75mg/kg infusion over 30 min
b Half-dose tenecteplase administered in patients ≥ 75 years old
c Reteplase administered as two boluses of 10 million units given 30 minutes apart
Conclusions
- Evidence supports PCI is the first line option for management of patients requiring reperfusion during cardiac arrest when a STEMI is suspected
- Available evidence suggests tenecteplase and alteplase are appropriate fibrinolytic therapies when PCI is unavailable
- Tenecteplase is an alternative fibrinolytic therapy and has been evaluated safe and efficacious as a bolus dose of 30-50mg
- When alteplase is the only fibrinolytic therapy available, there is data to support bolus therapy +/- a weight based infusion during cardiac arrest
- Thrombolytic agents administered during CPR can improve the rate of survival but are associated with a risk of severe bleeding
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