Clot Limiting vs. Clot Busting: The Role of Catheter-directed Thrombolysis in Treating Intermediate- to High-risk Pulmonary Embolism

A 68-year-old man was admitted to the orthopedics service with a femoral fracture, which had been managed nonoperatively. On the third day of admission, the patient experienced sudden shortness of breath and right-sided pleuritic chest pain and was found to be hypoxemic. He became transiently hypotensive, but his blood pressure improved without intervention. A computed tomography pulmonary angiogram demonstrated right-sided pulmonary embolism (PE). Bedside echocardiogram revealed right ventricular (RV) dilatation and interventricular septum bowing. Laboratory investigations revealed an elevation in troponin. The hematology service was consulted and considered the following options: treating the patient with anticoagulation alone, performing systemic thrombolysis (ST), or involving interventional radiology for catheter-directed thrombolysis (CDT).

PE is a leading cause of morbidity and mortality across the world.¹  With clinical presentations ranging from asymptomatic to involving hemodynamic compromise and sudden death, a risk-stratified approach to treatment is essential.²  As per the American Heart Association and the European Society of Cardiology (ESC), an acute PE is considered high-risk (or massive) if there is associated persistent hemodynamic instability, while low-risk PE constitutes patients who are stable and without resulting cardiac dysfunction. The definition of intermediate-risk (or submassive) PE includes hemodynamically stable patients (PE Severity Index [PESI] III-VI or simplified PESI score of ≥1) and either elevated cardiac biomarkers or RV dysfunction.^2,3 

The approach to treating PE involves anticoagulation, ST, or CDT, depending on risk stratification as defined above.^2,4  High-risk PE is treated with ST followed by anticoagulation, while low-risk cases are treated with anticoagulation alone. Due to the paucity of studies examining CDT therapy, there is uncertainty as to its safety and efficacy, especially in intermediate- and high-risk cases.^5,6  The American Society of Hematology’s 2020 guidelines for PE suggest using systemic thrombolysis rather than CDT in patients with PE in whom thrombolysis is considered appropriate, similar to the approach suggested by the CHEST Guideline and Expert Panel Report.⁴  The ESC suggests using CDT in patients with high-risk PE in whom thrombolysis has failed or is contraindicated, or in low-risk patients who have failed anticoagulation therapy.²  This meta-analysis compared the safety and efficacy of different therapeutic strategies (anticoagulation, ST, and CDT) in patients with intermediate- or high-risk acute PE.

David Planer, MD, and colleagues analyzed 44 studies (including 19 randomized controlled trials [RCTs]) that examined therapeutic options for PE. They demonstrated with moderate certainty that CDT was associated with a lower risk of death than ST and anticoagulation alone (odds ratio [OR] 0.43, 95% CI 0.32-0.57); a lower risk of intracerebral hemorrhage than ST (OR 0.44, 95% CI 0.29-0.64); and a similar risk of intracerebral hemorrhage (OR 1.33, 95% CI 0.63-2.79) and major bleeding (OR 1.24, 95% CI 0.88-1.75) to anticoagulation alone.

Strengths of this study include strict quality-control protocol and relatively large sample size. There was significant heterogeneity in the method of CDT (including fragmentation and ultrasound use) as well as type and dose of thrombolytic used across the studies, which is a limitation in this analysis. Most studies included were observational with a small sample size.