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April 10, 2014

Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism.

Mazen Kherallah

Summarized by: 

What was the research question?

  • Does the addition of tenecteplase in normotensive patients with intermediate-risk pulmonary embolism without hemodynamic compromise, improve the composite outcome of death and haemodynamic decompensation compared with heparin alone?

How did they do it?

  • A multicenter, double-blinded, randomized, controlled trial in 76 sites in 13 countries.

  • 1005 normotensive patients with confirmed pulmonary embolism, right ventricular dysfunction, and elevated troponin (intermediate risk PE) were randomized to receive Tenecteplase (30-50 mg IV bolus) in addition to heparin infusion (506 patients) or placebo with IV heparin (499 patients).

  • Primary outcome was a composite outcome of hemodynamic decompensation or death within 7 days of randomization.

  • The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization.

What did they find?

  • The composite outcome of death or hemodynamic decompensation within 7 days was significantly lower in the Tenecteplase group compared to the placebo group (2.6% vs. 5.6%, P=0.02, NNT 34). The benefit was mainly driven by hemodynamic decompensation.

  • Mortality at 7 days was not significantly different in the Tenecteplase group compared to the placebo group (1.2% vs. 1.8%, P=0.42), or at 30 days (2.4% vs. 3.2%, P=0.42).

  • Haemodynamic decompensation was significantly lower in the Tenecteplase group compared to the placebo group (1.6% vs. 5%, P=0.002, NNT 30).

  • Major extracranial bleeding was significantly higher in Tenecteplase group compared to placebo (6.3% vs. 1.2%, P<0.001, NNH 19) and same for  hemorrhagic stroke (2% vs 0.2%, P=0.003, NNH 55)

  • Major extracranial bleeding was numerically lower in pre-defined subgroup of patients who were ≤75 years compared to >75 years (11.1% vs. 4.1%, P=0.09).

Are there any limitations?

  • Composite outcome is not favored.

  • Not powered for mortality benefit.

  • Inclusion criteria of up to 15 days after PE would question that the risks of Tenecteplase would outweigh the benefits.

  • Does not exclude the benefit of lower dose of Tenecteplase.

  • There was a higher rate of use of LMWH/fondaparinux in the Tenecteplase group prior to randomization.

What does it mean?

  • Among patients with intermediate risk pulmonary embolism, the use of Tenecteplase in addition to heparin reduces hemodynamic compensation but increases the risk of major bleeding.

  • This study does not support the use of thrombolysis in submassive PE.


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