Clinical question: Do fibrinolytics decrease mortality rates in intermediate-risk pulmonary emboli?
Background: Over the past 40 years, fibrinolytics have been studied in fewer than 1,000 patients with pulmonary emboli. Previous studies have shown improvement in hemodynamic response, though the evidence for clinical outcomes such as death and hemodynamic collapse have not been studied adequately in intermediate-risk pulmonary emboli.
Study design: Randomized, double-blinded, placebo-controlled trial.
Setting: Seventy-six sites in 13 countries.
Synopsis: The PEITHO [Pulmonary EmbolIsm THrOmbolysis] trial randomized 1,006 patients in a double-blind fashion. All patients had acute pulmonary emboli with evidence of right ventricular dysfunction on computed tomography scan or echocardiogram, as well as an elevated troponin, in the absence of hemodynamic compromise. Patients received tenecteplase and heparin or placebo and heparin. The primary outcome was death and hemodynamic decompensation.
The primary outcome was found in 2.6% of the treatment group and 5.6% in the placebo group (P=0.02), favoring the treatment group; however, there was no difference in death at seven days (1.2% vs. 1.8%; P=0.42) and 30 days (2.4% vs. 3.2%; P=0.42). Additionally, there were higher rates of extracranial bleeding (6.3% vs. 1.2%; P=<0.001) and stroke (2.4% vs. 0.2%; P=0.003) in the tenecteplase group than in the placebo group. Of the 12 strokes in the treatment group, 11 were hemorrhagic.
Bottom line: Treatment of intermediate-risk pulmonary emboli with fibrinolytics may improve hemodynamics; however, there is no mortality benefit, and fibrinolytic therapy carries an increased risk of bleeding and stroke.
Citation: Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411.