New Trials Favor PE Intervention in Sicker Intermediate-Risk Patients

Recent randomized trials in intermediate-high-risk pulmonary embolism (PE) support catheter-based intervention over anticoagulation alone, particularly in patients with added markers of clinical severity, according to Samantha Pettigrew, MD, assistant professor of clinical thoracic medicine at the Lewis Katz School of Medicine at Temple University.

Pettigrew spoke with HCPLive at the CHEST 2026 Annual Meeting in Phoenix, Arizona, held October 18-21, after presenting in the Pulmonary Vascular Disease Section session "Pulmonary Embolism Care in 2026: New Randomized Clinical Trials and What's Coming Next."¹ The session reviewed HI-PEITHO, STORM-PE, PEERLESS, and other trials reported in the past year.

"So I think in choosing your patients, if you have somebody who you are a little bit more worried about than usual, if it is just not sitting right, maybe if they do not fit very clearly into the guidelines we have out right now, thinking about escalating their care, talking to them about intervention, talking to your interventionalists is really important," Pettigrew said.

HI-PEITHO randomized 544 patients with intermediate-high-risk PE plus tachycardia, low systolic blood pressure without shock, or hypoxemia to ultrasound-facilitated catheter-directed thrombolysis or anticoagulation alone.² The composite of PE-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrent PE occurred in 4.0% versus 10.3% of patients, driven by fewer decompensation events, with no significant difference in major bleeding or all-cause death.

PRAGUE-26 applied the standard intermediate-high-risk definition in 558 patients, and the 7-day composite of death, recurrent PE, or cardiorespiratory decompensation or collapse occurred in 0.7% with catheter-directed thrombolysis versus 6.8% with anticoagulation alone (relative risk, 0.10; 95% CI, 0.02–0.44).³ For patients without added severity markers, Pettigrew said bleeding risk assessment carries more weight in the decision to intervene.

In PEERLESS, the first head-to-head randomized comparison of catheter-based therapies, large-bore mechanical thrombectomy outperformed catheter-directed thrombolysis on a hierarchical win ratio (5.01; 95% CI, 3.68–6.97; P < .001), driven by lower ICU utilization, the lowest-ranked component.⁴ Excluding ICU outcomes, the win ratio was 1.34 (95% CI, 0.78–2.35; P = .30). Pettigrew noted no trial has yet shown a mortality benefit, though she said reduced ICU use matters for hospital flow and for limiting delirium and infection risk.

References

1. Pulmonary embolism care in 2026: new randomized clinical trials and what's coming next. Session presented at: CHEST 2026 Annual Meeting; October 18-21, 2026; Phoenix, AZ.

2. Konstantinides SV, et al. Ultrasound-facilitated catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: primary results of the HI-PEITHO randomized clinical trial. N Engl J Med. Published online March 28, 2026.

3. Kroupa J, Radvan M, Mrozek J, et al. Catheter-directed thrombolysis in intermediate-high-risk pulmonary embolism. N Engl J Med. Published online 2026.

4. Jaber WA, Gonsalves CF, Stortecky S, et al. Large-bore mechanical thrombectomy versus catheter-directed thrombolysis in the management of intermediate-risk pulmonary embolism: primary results of the PEERLESS randomized controlled trial. Circulation. 2025;151(5):260-273.