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PEITHO

"Tenecteplase in Normotensive Patients with Pulmonary Embolism". The New England Journal of Medicine. 2014. 370(15):1402-1411. PubMed

Links to original sources: Wiki Journal Post Full Journal Article

Clinical Question


In normotensive patients with intermediate-risk pulmonary embolism, does treatment with tenecteplase in addition to anticoagulation improve clinical outcomes?

Bottom Line


In normotensive patients with intermediate-risk pulmonary embolism, tenecteplase treatment reduced the primary composite outcome of death or hemodynamic decompensation compared to placebo, but increased the risk of major hemorrhage and stroke.

Major Points


Fibrinolytic therapy for pulmonary embolism (PE) is debated, particularly for patients with intermediate-risk PE who are normotensive but have right ventricular dysfunction or myocardial injury. The Pulmonary Embolism Thrombolysis (PEITHO) trial assessed the role of the fibrinolytic agent tenecteplase in this patient population.

Guidelines


As of the last knowledge update, specific guidelines reflecting the results of this trial were not referenced.

Design


- Multicenter, double-blind, placebo-controlled randomized trial - N=1,005 participants with intermediate-risk PE - Tenecteplase + heparin (n=506) - Placebo + heparin (n=499) - Setting: 76 sites in 13 countries - Enrollment: November 2007 to July 2012 - Follow-up: 30 days - Analysis: Intention-to-treat - Primary outcome: Death or hemodynamic decompensation within 7 days

Population


Inclusion Criteria: - Age ≥18 years - Confirmed acute PE with symptom onset within 15 days - Echocardiography or CT showing right ventricular dysfunction - Positive cardiac troponin I or T test

Exclusion Criteria: - Systolic blood pressure <90 mm Hg or drop ≥40 mm Hg for >15 minutes - Active internal bleeding - Ischemic stroke within preceding 2 months

Baseline Characteristics: - Median age: 70 years - Female: 44.5% - Normotensive at randomization

Interventions


- Tenecteplase: single weight-based intravenous bolus (30-50 mg) - Placebo: intravenous bolus of the same volume and appearance as tenecteplase - Both groups received unfractionated heparin according to protocol

Outcomes


Primary Outcomes: - Death or hemodynamic decompensation within 7 days: 2.6% (tenecteplase) vs. 5.6% (placebo); OR 0.44 [95% CI, 0.23 to 0.87]; P=0.02

Secondary Outcome: - Death within 7 days: 1.2% vs. 1.8%; P=0.42 - Death within 30 days: 2.4% vs. 3.2%; P=0.42

Criticisms


- Study not powered to detect differences in death rates, which were infrequent. - Hemodynamic decompensation had a broad definition, including persistent hypotension without overt clinical compromise. - Intracranial and major bleeding rates may limit the practical use of fibrinolytic therapy in intermediate-risk PE.

Funding


Supported by Programme Hospitalier de Recherche Clinique in France, the Federal Ministry of Education and Research in Germany, and a grant from Boehringer Ingelheim.

Further Reading


- Konstantinides, Stavros V., et al. "Fibrinolysis for patients with intermediate-risk pulmonary embolism." New England Journal of Medicine 370.15 (2014): 1402-1411.