What is the comparison between Alteplase (tissue plasminogen activator) and Tenecteplase in the treatment of pulmonary embolism?

Alteplase vs Tenecteplase in Pulmonary Embolism

Tenecteplase is superior to alteplase for intermediate-risk pulmonary embolism due to its more favorable safety profile and comparable efficacy, while alteplase remains the preferred agent for massive pulmonary embolism requiring rapid intervention. 1

Comparison of Mechanisms and Administration

• Both alteplase and tenecteplase are tissue plasminogen activators (tPAs) that promote clot dissolution, but tenecteplase has a longer half-life allowing for bolus administration rather than continuous infusion 1, 2
• Alteplase requires a 2-hour infusion (100mg total dose), while tenecteplase can be administered as a single bolus, offering greater convenience in emergency settings 1, 3
• The FDA-approved dose of alteplase for massive PE is 100 mg administered as a continuous intravenous infusion over 2 hours 3

Efficacy Comparison

• The PEITHO trial, the largest randomized controlled trial of thrombolysis in intermediate-risk PE, demonstrated that tenecteplase decreased the frequency of hemodynamic collapse compared to anticoagulation alone (1.6% versus 5.0%; P=0.002) 1
• Tenecteplase showed improved right ventricular function in patients with intermediate-risk PE in the Becattini et al. study, though this trial was underpowered to detect differences in clinical outcomes 1
• A 2023 Bayesian network meta-analysis found that alteplase was superior to heparin in reducing mortality, recurrent PE, and pulmonary artery systolic pressure, while tenecteplase did not show a significant mortality benefit compared to anticoagulation alone 4

Safety Profile

• In the PEITHO trial, tenecteplase was associated with a 2% incidence of hemorrhagic stroke (versus 0.2% in the placebo arm) and increased major non-intracranial bleeding (6.3% vs. 1.5%; P<0.001) 1
• The 2023 meta-analysis found that tenecteplase had a higher incidence of minor bleeding compared to heparin (RR = 3.27,95% CI, 1.36,7.39) and streptokinase (RR = 3.22,95% CI, 1.01,11.10) 4
• Low-dose alteplase regimens have been studied to reduce bleeding complications, particularly in patients at higher risk of bleeding, including elderly patients 5

Clinical Decision Algorithm

For Massive PE (hemodynamically unstable):

1. Alteplase remains the standard FDA-approved agent (100mg over 2 hours) 3
2. Consider reteplase as an alternative (administered as 2 intravenous bolus injections of 10 U 30 minutes apart), which has shown comparable efficacy to alteplase in reducing pulmonary vascular resistance 2

For Intermediate-Risk PE (hemodynamically stable with RV dysfunction):

1. Tenecteplase should be considered first-line when thrombolysis is indicated, due to its convenient single-bolus administration 1
2. Consider low-dose alteplase regimens in patients with higher bleeding risk (particularly those <65kg or elderly) 5
3. For patients with contraindications to systemic thrombolysis, catheter-directed thrombolysis with low-dose alteplase may be considered 1

Special Considerations

• Ultrasound-assisted catheter-directed thrombolysis (USAT) with alteplase (20mg total) has shown efficacy in reducing RV/LV ratio in intermediate-risk PE patients 1
• The timing of thrombolysis is important - greatest benefit is observed when treatment is initiated within 48 hours of symptom onset, though it may still be useful up to 6-14 days 1
• In life-threatening PE, contraindications to thrombolysis may need to be reconsidered given the high mortality rate without treatment 3

Pitfalls and Caveats

• Avoid using tenecteplase in patients with high bleeding risk, as it appears to have a higher bleeding risk profile compared to other thrombolytics 4
• Do not delay treatment of massive PE while awaiting confirmatory imaging if clinical suspicion is high and bedside echocardiography shows RV dysfunction 3
• Remember that anticoagulation with heparin should be withheld during the 2-hour alteplase infusion period but resumed afterward 3
• Be aware that most studies on thrombolytics in PE have excluded patients with hemodynamic instability, limiting direct evidence for massive PE 1