April 10, 2014
Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism.
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.