Pulmonary embolism
Most of us would agree that massive PE is treated with fibrinolysis and non-massive PE is treated with anticoagulation. The area of great debate has been the optimal treatment for sub-massive PE. The MOPETT Trial was published in January 2013 and although the patient population was small, it did show a huge benefit in pulmonary pressures at 28 months with fibrinolysis. The next study we have all been waiting for is the Pulmonary Embolism Thrombolysis (PEITHO) trial, which was just published yesterday in the NEJM, evaluating fibrinolysis for patients with intermediate-risk PE.


Half of the cases of pulmonary embolism (PE) in the United States are diagnosed in the Emergency Department and follow ACS as the second most common cause of sudden unexpected death in outpatients. PE is typically broken down into three major categories:

  • Massive PE: Hemodynamic compromise with a systolic blood pressure of <90 mmHg
  • Sub-Massive PE: No hypotension but right ventricular strain or myocardial necrosis
  • Non-Massive PE: No hemodynamic compromise and no RV strain

Article Overview1

The purpose of this study was to determine the clinical efficacy and safety of fibrinolytic therapy with a single-bolus injection of tenecteplase, in addition to standard anticoagulation therapy in normotensive patients with an intermediate-risk PE.

Intermediate-risk PE was defined as acute RV dysfunction and myocardial injury without overt hemodynamic compromise.

What they did:

  • Randomized, double-blind, placebo-controlled trial of 1,005 patients with “intermediate-risk” PE
  • 76 sites in 13 countries
  • Tenecteplase plus heparin vs placebo plus heparin
  • Patients were eligible if they had ALL of the following:
    • Age ≥ 18 years
    • Confirmed PE with onset within 15 days
    • RV dysfunction (diagnosed on echocardiography and/or CT)
    • Myocardial injury (diagnosed with positive cardiac troponin I or T)

Treatment regimens:

  • Treatment arm: Weight-based tenecteplase (range: 30 – 50 mg) given as an IV bolus + standard anticoagulation
  • Control arm: Placebo + standard anticoagulation

Primary outcomes:

  • Death or hemodynamic decompensation within 7 days after randomization

Safety outcomes:

  • Extracranial major bleeding within 7 days after randomization
  • Ischemic or hemorrhagic stroke within 7 days 
  • Serious adverse events within 30 days


OutcomeTenecteplase GroupPlacebo GroupP Value
Death at 7 days1.2%1.8%0.42
Hemodynamic compromise at 7 days1.6%5.0%0.002
Extracranial bleeding at 7 days6.3%1.2%<0.001
Stroke at 7 days2.4%0.2%0.003
Death at 30 days2.4%3.2%0.42


  • There is no mention of pulmonary pressures in the results


In normotensive patients with intermediate-risk PE, death and hemodynamic decompensation are reduced with treatment of tenecteplase, but there is also a significant associated risk for intracranial and other major bleeding.

My thoughts

  • Fewer patients in the tenecteplase group developed persistent hypotension (1.5% vs 3.6%), required catecholamines (0.59% vs 2.8%), mechanical ventilation (1.6% vs 3.0%), or cardiopulmonary resuscitation (0.19% vs 1.0%).
  • The paper states that the risk of bleeding in younger patients is lower compared to older patients; however, patient subgroup analysis used an arbitrary pre-specified age (≤ 75 years vs > 75 years) showing a slightly greater risk for major extracranial bleeding in older patients. This risk, however, was not statistically significant (p=0.09).
  • Although the risk of EXTRAcranial bleeding was lower in the ≤ 75 years group, there was no mention of decreased INTRAcranial hemorrhage in this group as well. So it is unclear if there was a difference in overall bleeding complications between the age groups.
  • Would have liked to see a “safe dose” or “reduced dose” strategy studied here.

Clinical Bottom Line

Per these PEITHO results, there was a significant increase in hemorrhagic complications with full dose tenecteplase in intermediate-risk PEs. The treatment, however, was also associated with a slight clinical benefit.

We concur with the accompanying NEJM editorial.2 In brief, the results suggest that acute PE patients WITHOUT overt hemodynamic compromise should be carefully monitored and receive standard anticoagulation only (despite demonstrating RV dysfunction and myocardial injury) given the low mortality rate of 1.8% in the placebo group. Rescue thrombolytics can be considered once patients demonstrate hemodynamic instability. The risk of GIVING thrombolytics may be lower than NOT GIVING thrombolytics at this point.

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. [PubMed]
Elliott C. Fibrinolysis of pulmonary emboli–steer closer to Scylla. N Engl J Med. 2014;370(15):1457-1458. [PubMed]
Salim Rezaie, MD

Salim Rezaie, MD

ALiEM Associate Editor Clinical Assistant Professor of EM and IM University of Texas Health Science Center at San Antonio Founder, Editor, Author of R.E.B.E.L. EM and REBEL Reviews