Ultrasound-Facilitated Catheter-Directed Fibrinolysis Reduces Early Decompensation in Pulmonary Embolism

Ultrasound-facilitated, catheter-directed fibrinolysis combined with anticoagulation significantly reduced the risk of early clinical deterioration compared with anticoagulation alone in patients with acute, intermediate-risk pulmonary embolism (PE), according to results of the HI-PEITHO trial.

Published in the New England Journal of Medicine and simultaneously presented at the American College of Cardiology's Annual Scientific Session (ACC.26), findings provide the first randomized controlled trial evidence supporting a catheter-based intervention strategy over anticoagulation alone for this specific and challenging patient population.1

"This trial shows that a catheter intervention can indeed be effective and improve the prognosis for patients with severe PE and elevated risk of early death or life-threatening complications," said lead investigator Stavros V. Konstantinides, MD, PhD, of the University Medical Center of the Johannes Gutenberg University in Mainz, Germany.2 "If the right patients are selected for this procedure, it can prevent patients from deteriorating and it can do so at an acceptably low risk of bleeding complications."

HI-PEITHO Trial Design and Patient Population

HI-PEITHO was a multinational, adaptive-design, open-label, randomized trial with blinded outcome adjudication conducted at 59 sites in the United States and 8 European countries. The trial was conducted as a tripartite partnership between Boston Scientific, the University Medical Center of the Johannes Gutenberg University Mainz, and the PERT Consortium.

The trial enrolled 544 patients with acute, intermediate-risk PE confirmed by CT pulmonary angiography, with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of 1.0 or higher, elevated troponin, and at least 2 criteria for cardiorespiratory distress:

• Systolic blood pressure of 110 mmHg or lower
• Heart rate of 100 or more beats per minute
• Respiratory rate exceeding 20 breaths per minute

Of note, patients with persistent hemodynamic instability, considered as those meeting criteria for high-risk, overt shock, were excluded.

The study cohort had a mean age of 58.2 (SD, 13.5) years, 42.6% were women, and the mean National Early Warning Score at baseline was 6.0. Patients were randomized 1:1 to ultrasound-facilitated, catheter-directed fibrinolysis with alteplase using the EkoSonic endovascular system plus anticoagulation, or anticoagulation alone.1

The primary outcome of interest for the trial was incidence of PE-related death, cardiorespiratory decompensation or collapse, or symptomatic PE recurrence within 7 days.1

Investigators pointed out the fibrinolysis protocol was standardized, with the the mean total dose of alteplase approximately 16.9 mg for bilateral catheter placement over a mean infusion duration of 7.2 hours. Randomization and initiation of assigned therapy were required within 6 hours of confirmed PE and fulfillment of risk criteria.1

Primary Outcome and Safety Results

The primary composite outcome occurred in 11 patients (4.0%) in the intervention group versus 28 patients (10.3%) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = .005). Results suggested the benefit was driven primarily by a reduction in cardiorespiratory decompensation or collapse (3.7% vs 10.3%), while PE-related death and recurrence did not differ significantly between groups.1

Rescue therapy was required in 2.9% of intervention group patients versus 9.2% of control group patients. Mean hospital length of stay was numerically shorter in the intervention group (5.77 vs 6.48 days), and mean ICU duration was modestly lower (2.19 vs 2.78 days), though confidence intervals for both crossed 0.1

With respect to safety, major bleeding by ISTH criteria occurred in 4.1% of intervention group patients and 3.0% of control group patients at 30 days (RR, 1.4; 95% CI, 0.6 to 3.4; P = .64).1

Investigators pointed out no intracranial hemorrhage occurred in either group, a finding highlighted as distinguishing this catheter-directed, low-dose approach from the systemic fibrinolysis regimens historically associated with prohibitive rates of intracranial bleeding in this risk category.1

Limitations and Ongoing Follow-up

The investigators called attention to several limitations in their manuscript. These included randomization being open-label, introducing potential expectation bias in treatment escalation decisions, and the trial not being powered to detect differences in bleeding complications or to conduct subgroup analyses.1

Additionally, only 10.1% of patients were aged 75 or older, limiting generalizability to older and frailer populations. Randomization was not stratified by site, precluding exclusion of center-level effects. Results are specific to the EkoSonic system and the standardized alteplase protocol used in this trial and should not be extrapolated to other catheter-based PE treatment approaches.1

Of note, the 12-month patient follow-up is ongoing to evaluate long-term survival, functional outcomes, quality of life, and health care utilization. The investigators also noted HI-PEITHO, alongside contemporaneous trials testing mechanical thrombectomy and reduced-dose systemic fibrinolysis in similar populations, may together provide the comparative evidence base needed to inform future guideline recommendations for intermediate-risk PE management.1

References:

1. Rosenfield K, Klok FA, Piazza G, et al. Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism. New England Journal of Medicine. Published online March 28, 2026. doi: 10.1056/NEJMoa2516567

2. American College of Cardiology. Catheter-Based Procedure Improves Pulmonary Embolism Outcomes - American College of Cardiology. American College of Cardiology. Published March 28, 2026. Accessed March 28, 2026. https://www.acc.org/About-ACC/Press-Releases/2026/03/28/14/11/Catheter-Based-Procedure-Improves-Pulmonary-Embolism-Outcomes