Research Consensus Panel Follow-up: 8-Year Update on Submassive Pulmonary Embolism

Clinical Question

What is the current state of endovascular pulmonary embolism practice and the Pulmonary Embolism–Thrombus Removal with Catheter-Directed Therapy trial, now 8 years since the 2015 Research Consensus Panel?

Take Away Point

The article discussed the catheter-directed therapy (CDT) trials and their outcomes since the 2015 Research Consensus Panel. Catheter-directed lysis (CDL) studies showed reduction in RV/LV ratio but inconsistent major bleeding rates. Mechanical thrombectomy (MT) studies demonstrated safety and effectiveness but lack comparison to AC alone. PE-TRACT and other upcoming randomized clinical trials (RCT) will define role of CDT in submassive PE.

Reference

Research Consensus Panel Follow-up: 8-Year Update on Submassive Pulmonary Embolism. Sista et al. Journal of Vascular and Interventional Radiology, Volume 34, Issue 10, P1658-1663, 10.1016/j.jvir.2023.06.032

Study Design

Narrative Review

Funding Source

The authors of this article report grants and funding from various organizations, including the NIH, AngioDynamics, Cook Medical, Boston Scientific, Gore, Medtronic, Penumbra, Becton Dickinson, Philips, Cordis, Bayer, NHLBI, BMS, Janssen, and Pfizer.

Setting

United States

Figure 2
Completed, Enrolling, and Upcoming Randomized Controlled Trials

Summary

In 2015, a panel of 19 pulmonary embolism (PE) experts from multiple disciplines convened to discuss the current knowledge and determine the future questions that need to be answered. This article is a follow-up to the 2015 Research Consensus Panel (RCP), discussing what has changed since then. Several consequential studies of catheter-directed therapy (CDT) have been published, and two mechanical thrombectomy devices have been cleared by the FDA to treat PE. In addition, the PE-TRACT trial has begun enrolling patients.

Several catheter-directed thrombolysis (CDL) trials and studies have been published. The article briefly discusses trials such as the ULTIMA, SEATTLE II, OPTALYSE, RESCUE, PEERLESS, SUNSET, and CANARY. All of which evaluated different aspects of CDL, including dosing, duration, and associated thrombus clearance. Despite promising results reported in some studies, limitations, such as low power and variable dosing were noted. Most trials demonstrated a reduction in the right ventricular to left ventricular ratio with CDL. Major bleeding rates were inconsistent across the different trials, up to 10% in SEATTLE II. Some concluded no significant difference in outcomes between CDL and standard treatment of anticoagulation (CANARY). Of note, SUNSET demonstrated no difference in thrombus clearance or bleeding between US-assisted and standard CDL.

Mechanical thrombectomy (MT) serves as an alternative to CDL in treating PE. Since the RCP, several studies, including the FLARE and EXTRACT trials, have looked at the efficacy of MT. These studies specifically evaluated two FDA-cleared devices, the Flowtriever and the Indigo Aspiration System, respectively. Both of these have shown promising results in single-arm trials, including reduction in right ventricular to left ventricular ratio, similar to those of CDL in prior published studies, and low major adverse event rates. However, the studies were limited by low power and a lack of anticoagulation-only control groups. The PEERLESS II and STORM-PE trials aim to compare mechanical thrombectomy devices to anticoagulation alone.

The 2015 RCP emphasized the critical need for rigorous study of CDT for submassive PE. Two complementary randomized clinical trials are ongoing. The HI-PEITHO trial seeks to evaluate ultrasound-guided CDL plus anticoagulation versus anticoagulation alone. The second study, the PE-TRACT trial, stems from the 2015 RCP incorporating many of the clinical questions and goals discussed by the PE experts. It is a phase III, multicenter, randomized, open-label, 2-arm controlled clinical trial. The study will evaluate two primary outcomes: the first being physiologic outcomes measured by peak oxygen uptake during cardiopulmonary exercise testing at 3 months; the second being patient-reported functional outcomes measured at 12 months. The study aims to enroll 500 patients across 30-50 clinical sites in the US, with completion expected by the end of 2026. 

Commentary

This article is an informative narrative review of the current state of knowledge on submassive pulmonary embolism. The authors briefly outlined the specific questions identified by the RCP as high interest and high impact. Additionally, the authors described the primary outcomes and limitations of the studies that followed the 2015 RCP. Furthermore, the authors analyzed the study designs of the upcoming trials. As a narrative review and update to the 2015 RCP, this article effectively presents the current knowledge and upcoming research concerning submassive PE treatment. Moving forward, the next step would likely involve conducting a comprehensive systematic review to provide robust, objective data and insights in study design for future studies focusing on submassive PE. Overall, the authors accomplished their goal of providing a summary of the current state of knowledge on submassive PE as well as providing key insights into the future direction of research.

Post Author

Aric Patel, MS
OMS IV
University of New England
College of Osteopathic Medicine