Large-bore mechanical thrombectomy (LBMT) was superior to catheter-directed thrombolysis (CDT) for treatment of intermediate-risk pulmonary embolism (PE), based on data from 550 individuals presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting.

“Intermediate-risk pulmonary embolism represents a critical therapeutic gray zone where clinicians need interventions that are both effective and safe,” said lead author Krunal H. Patel, MD, fellow in the Department of Thoracic Surgery and Medicine at the Temple University Hospital, Philadelphia, in an interview.

Historically, CDT has been the primary minimally invasive option for intermediate-risk PE, but it carries inherent bleeding risks and often requires ICU monitoring, said Patel, who presented the findings at the meeting.

LBMT could offer a safer, more efficient, and equally effective or superior alternative, but comparison data for the two procedures to guide clinical decision-making were lacking, said Patel.

In a study known as the PEERLESS trial, Patel and colleagues randomized 274 acute intermediate-risk PE patients to LBMT and 276 to CDT. The study also included a nonrandomized cohort of 142 patients with absolute contraindications to thrombolytics who were treated with LBMT. The mean age of the participants in these groups was approximately 64, 61, and 64 years, respectively, and more than 70% of patients in each group were White. The study included patients from 57 sites in the US, Germany, and Switzerland.

The primary endpoint was a win ratio of five outcomes including all-cause mortality, intracranial hemorrhage, major bleeding, clinical deterioration and/or bailout, and stay in post-procedural intensive care through discharge or 7 days.

The most dramatic differences between the LBMT and CDT procedures were the reduction in clinical deterioration (1.8% vs 5.4%; P = .0378), with 3.5% in the contraindication group, and ICU admissions (41.6% vs 98.6%), which exceeded the researchers’ expectations, Patel told Medscape Medical News.

Interventional serious adverse events were defined as those related to the endovascular procedure, device, and/or thrombolytic medication. The most frequent interventional serious adverse event was vascular access site hematoma in the LBMT and CDT groups (2.2% and 2.5%, respectively), and blood loss anemia was the most frequent interventional serious adverse event in the contraindication cohort (2.1%).

A total of four patients in the LBMT group experienced deterioration during the procedure, but all cases were resolved the same day. Of these, three were the result of hypotension, and one was a need for additional oxygen. None of the deteriorations in the LBMT group involved cardiac arrest or arrhythmia. By contrast, 10 patients in the CDT group experienced deteriorations post-procedure that lasted out to 6 days and included cardiac and hypotension events. Five patients in the contraindication cohort experienced deteriorations involving hypotension, on the day of the procedure and one on the following day.

Bailouts occurred in one patient in the LBMT group, six patients in the CDT group, and no patients in the contraindication group. The mean time to first deterioration/bailout was significantly lower in the LBMT group than in the CDT group (0 days vs 2.1 days; P = .0025) and 0.2 days in the contraindication group.

Major bleeding rates were similar in the LBMT, CDT, and contraindication groups (6.9%, 6.9%, and 7.0%, respectively). The mean times to first major bleeding event for the groups were 1.3, 1.6, and 1.0 days post-procedure, respectively.

The proportion of major bleeding events caused solely by hemoglobin drop and/or transfusion was 90.5%, 81.0%, and 84% for the LBMT, CDT, and contraindication cohort, respectively.

The findings were limited by the inclusion of patients from a single center, but the patients managed with LBMT experienced fewer and less severe clinical deteriorations and bailouts, and earlier resolution of deterioration than those managed with CDT, with similar major bleeding rates, the researchers concluded.

“The magnitude of benefit with LBMT was impressive; a primary win ratio of 5.01 is a strong and clear signal,” said Patel. “While prior observational studies hinted at LBMT’s potential, seeing this level of superiority in a randomized trial reinforces its strength as a frontline therapy,” he added.

Although the researchers anticipated that LBMT would avoid some of the bleeding risks associated with thrombolysis, the dramatic reductions exceeded expectations, which speaks not only to procedural safety but also to a smoother recovery, which has additional implications for the patient experience and the use of hospital resources, he added.

Clinical Implications

“LBMT is emerging as a game-changing therapy for intermediate-risk PE,” said Patel. “The PEERLESS trial shows that it can deliver superior clinical stability, dramatically reduce ICU utilization, and maintain low bleeding rates — even in patients at high bleeding risk,” he said.

In clinical practice, the findings support moving LBMT toward the forefront of interventional PE care in hospitals with PE response team infrastructure and LBMT capability, Patel told Medscape Medical News. “LBMT offers clinicians the ability to intervene decisively without exposing patients to systemic or local thrombolytics, making it particularly valuable in fragile populations,” he noted.

Next Steps in Patient Selection and Long-Term Data

Future research is needed to examine whether the short-term benefits seen in the PEERLESS study extend to the long-term, including right ventricular recovery, functional capacity, and prevention of chronic thromboembolic pulmonary hypertension, Patel told Medscape Medical News. Other valuable studies would refine patient selection algorithms and identify those who would benefit most from LBMT, examine the economic impact and resource optimization of LBMT, and compare LBMT standard of care with anticoagulation, he said.

“But even now, these results make a strong case for reevaluating how we approach interventional PE care, with LBMT leading that evolution,” Patel said.

The study received no outside funding. Patel had no financial conflicts to disclose.