Safety and efficacy of thrombolytic interventions in the treatment of intermediate and high-risk pulmonary embolism

BACKGROUND: Intermediate to high-risk pulmonary embolism management is controversial in the absence of hemodynamic instability. Anticoagulation with systemic thrombolysis is commonly employed in these patients, and alternative interventional therapies when contraindications to thrombolysis are present. No comparative evidence exists between systemic alteplase, tenecteplase and catheter directed thrombolysis (CDT) and practice continues to be clouded by this lack of literature. RESEARCH QUESTION: Does systemic alteplase, tenecteplase or CDT have better safety or efficacy outcomes in the treatment of intermediate to high-risk pulmonary embolism? STUDY DESIGN AND METHODS: This was a retrospective, multicenter study including patients 18-90 years old with an acute presentation of intermediate-high risk PE receiving systemic or directed thrombolysis with therapeutic anticoagulation. The primary outcome was major bleeding complications within 72 h of treatment. Secondary outcomes included minor bleeding, hemodynamic decompensation, 28-day ventilator-free days, mortality and length of stay. RESULTS: The primary outcome was significantly higher with tenecteplase and US-CDT when compared to alteplase (alteplase 10.9% vs. tenecteplase 31.1%, P = 0.004; US-CDT 21.4%, P = 0.03). After propensity matching, tenecteplase was associated with a higher rate of major bleeding ( P = 0.13) while US-CDT showed a significantly higher risk of complications ( P = 0.04). This was supported by multivariate logistic regression with alteplase vs. US-CDT (odds ratio 0.07; 95% confidence interval 0.01, 0.3). Tenecteplase receipt was not associated with different rates of hemodynamic decompensation or mortality compared to alteplase while US-CDT had significantly lower rates, likely secondary to acuity of illness. INTERPRETATION: Alteplase was associated with the lowest risk of major bleeding, but with variable disease severities. Selection of agent for the treatment of PE continues to require analysis of patient-specific hemodynamics and disease severity.