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evident
Original paper
2014NEJMEmergency Medicine

PEITHO

Fibrinolysis for patients with intermediate-risk pulmonary embolism

RCTPulmonary embolism

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Overview

In intermediate-risk PE, tenecteplase reduced hemodynamic collapse but increased major extracranial bleeding and stroke.

Clinical takeaway

PEITHO is why most intermediate-risk PE patients get anticoagulation alone: fibrinolysis can prevent decompensation, but the bleeding and stroke cost is high.

Key result

Death or hemodynamic decompensation at 7 days was 2.6% with tenecteplase vs 5.6% with placebo (OR 0.44).

Practice impact

Do not routinely lyse intermediate-risk PE; weigh a lower collapse rate against more major bleeding and stroke.

Evidence

Study design

Randomized, double-blind trial.

Enrollment

1,006

Follow-up

Death or hemodynamic decompensation within 7 days; mortality also reported through day 30.

Geography

Not listed

Clinical question

Does tenecteplase plus heparin reduce death or hemodynamic decompensation compared with heparin alone in intermediate-risk PE?

Population

  • Normotensive patients with intermediate-risk PE who had right ventricular dysfunction on echocardiography or CT and a positive troponin I or troponin T.

Intervention

Tenecteplase plus heparin.

Comparator

Placebo plus heparin.

Primary outcome

Death or hemodynamic decompensation (or collapse) within 7 days after randomization.

Tenecteplase reduced death or hemodynamic decompensation at 7 days but increased major extracranial bleeding and stroke.

Odds ratio / 0.44 / 95% CI 0.23-0.87 / p=0.02

Key results

  • Death or hemodynamic decompensation occurred in 2.6% with tenecteplase vs 5.6% with placebo; OR 0.44 (95% CI 0.23-0.87; P=0.02).
  • Death by day 7 was 1.2% vs 1.8% (P=0.42), and death by day 30 was 2.4% vs 3.2% (P=0.42).
  • Extracranial bleeding was 6.3% vs 1.2% (P<0.001).
  • Stroke occurred in 2.4% with tenecteplase (10 of 12 hemorrhagic) vs 0.2% with placebo (P=0.003).

Harms

  • Extracranial bleeding occurred in 6.3% with tenecteplase vs 1.2% with placebo (P<0.001).
  • Stroke occurred in 2.4% vs 0.2% (P=0.003) and was hemorrhagic in 10 of 12 tenecteplase strokes.

Clinical Use

Practice impact

  • Do not routinely lyse intermediate-risk PE; weigh a lower collapse rate against more major bleeding and stroke.

Applicability

  • Most applicable to normotensive patients with intermediate-risk PE who have both RV dysfunction and troponin elevation.

Limitations

  • The primary outcome mixed death and hemodynamic decompensation; death alone did not differ.
  • Eligible patients already had both RV dysfunction and myocardial injury.
  • The tenecteplase dose is not stated in the abstract.

Common misinterpretations

  • A positive primary outcome does not mean thrombolysis is indicated for all intermediate-risk PE.
  • This trial does not define management of high-risk PE with hypotension.

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. doi:10.1056/NEJMoa1302097

In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke.