Fibrinolysis for Intermediate-Risk PE: Increased Bleeding, No Mortality Effect

Clinical question

Does the use of fibrinolytic therapy improve mortality and morbidity in normotensive patients with acute pulmonary embolism who are at intermediate risk for adverse outcomes?

Bottom line

For patients with acute pulmonary embolism (PE) at intermediate risk for adverse outcomes, fibrinolytic therapy (tenecteplase plus standard anticoagulation) decreases the incidence of hemodynamic decompensation but does not decrease mortality as compared with anticoagulation alone. Not surprisingly, fibrinolysis also increases bleeding and strokes. You would need to treat 20 people with tenecteplase to cause one episode of bleeding, and 45 people to cause one additional stroke. Given the significant bleeding risk with this therapy, fibrinolysis in patients who are at higher risk of adverse outcomes but are hemodynamically stable cannot be recommended until further research shows a greater clinical benefit. (LOE = 1b)

Reference

Meyer G, Vicaut E, Danays T, et al, for the PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370(15):1402-1411.

Study design

Randomized controlled trial (nonblinded)

Funding source

Industry + govt

Allocation

Concealed

Setting

Inpatient (any location)

Synopsis

These authors enrolled adult patients with acute PE who were hemodynamically stable and were considered to have an intermediate risk for adverse outcomes as indicated by right ventricular dysfunction or myocardial injury. Right ventricular dysfunction was confirmed by either echocardiography or chest computed tomography, and myocardial injury was confirmed by a positive troponin test result. Using concealed allocation, investigators randomized these patients (N = 1006) to receive either fibrinolysis with tenecteplase at a weight-based dose or matching placebo. Both groups also received full anticoagulation with unfractionated heparin. Baseline characteristics were similar in the 2 groups and analysis was by intention to treat. Fewer patients in the tenecteplase group experienced the primary outcome of death or hemodynamic decompensation at 7 days (2.6% vs 5.6%; odds ratio = 0.44; 95% CI, 0.23 – 0.87). Looking at the individual components of the composite outcome, there was no significant difference in mortality between the 2 groups (1.2% vs 1.8%), but the tenecteplase group had a decreased incidence of hemodynamic decompensation (1.6% vs 5%; P = .002). The significance of this is unclear, as one of the definitions of hemodynamic decompensation was an isolated drop in systolic blood pressure to below 90 mmHg for at least 15 minutes. Major bleeding and hemorrhagic strokes were more common in the tenecteplase group (bleeding: 11.5% vs 2.4%; strokes: 2% vs 0.2%).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.