Research Summary

HI-PEITHO: Catheter-Directed Fibrinolysis in Pulmonary Embolism

Edited by:
Ashton L. Stahl

Key Highlights

  • In the HI-PEITHO trial, the 7-day primary composite outcome occurred in 4.0% of patients receiving ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation vs 10.3% with anticoagulation alone.
  • The benefit was driven mainly by fewer episodes of cardiorespiratory decompensation or collapse.
  • Major bleeding did not differ substantially between groups through 30 days, and no intracranial hemorrhage occurred in either group.

In a randomized trial published in The New England Journal of Medicine,1 ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation reduced the risk of a 7-day composite outcome of pulmonary embolism–related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism compared with anticoagulation alone in patients with acute, intermediate-risk pulmonary embolism. The study authors reported that the treatment effect was primarily attributable to less cardiorespiratory decompensation or collapse in the intervention group.

In their study, Rosenfield and colleagues1 conducted the multinational, adaptive-design HI-PEITHO trial at 59 sites in the United States and Europe from August 2021 through July 2025. Eligible adults aged 18 to 80 years had acute intermediate-risk pulmonary embolism confirmed on computed tomographic pulmonary angiography, a right ventricular-to-left ventricular end-diastolic diameter ratio of at least 1.0, elevated troponin, and at least 2 indicators of cardiorespiratory distress. Patients were randomly assigned 1:1 to ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation or to anticoagulation alone. The primary outcome was assessed within 7 days after randomization.

Study Findings

The intention-to-treat population included 544 patients, with 273 assigned to the intervention group and 271 to the control group. The mean age was 58.2 years, 42.6% were women, and 15.8% identified as non-White. A primary-outcome event occurred in 11 patients (4.0%; 95% CI, 2.3 to 7.1) in the intervention group and 28 patients (10.3%; 95% CI, 7.2 to 14.5) in the control group, for a relative risk of 0.39 (95% CI, 0.20 to 0.77; P = 0.005).

Cardiorespiratory decompensation or collapse occurred in 10 patients (3.7%) in the intervention group and 28 patients (10.3%) in the control group. Pulmonary embolism–related death occurred in 3 patients (1.1%) and 1 patient (0.4%), respectively, and the recurrence of pulmonary embolism occurred in 1 patient in each group. Major bleeding within 30 days occurred in 11 of 271 treated patients (4.1%) in the intervention group and 8 of 271 (3.0%) in the control group; no intracranial hemorrhage occurred in either group. Rescue therapy was used in 2.9% of the intervention group and 9.2% of the control group.1

Clinical Implications

According to the study authors, these findings suggest that ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation may improve short-term clinical outcomes in carefully selected patients with acute, intermediate-risk pulmonary embolism by reducing early decompensation. The authors also reported no apparent differences in major bleeding complications between groups.

The main limitations, as reported by the investigators, included nonblinded randomization, low overall event frequency that limited power for subgroup and bleeding comparisons, limited representation of older patients, potential center-level effects because randomization was not stratified by site, and uncertainty about generalizability to more ethnically diverse populations.

Expert Commentary

In their accompanying editorial published in New England Journal of Medicine,2 authors Alex C. Spyropoulos, MD, and Suresh Vedantham, MD, praised Rosenfield and colleagues for their work, while also cautioning that more research is still needed.

"Overall, the HI-PEITHO investigators should be congratulated for completing a challenging and important trial,” Drs Spyropoulos and Vedantham wrote in their editorial. “Their findings support a lower threshold for the use of ultrasound-facilitated, catheter-directed thrombolysis in patients with pulmonary embolism who would have been categorized as having intermediate-high risk or the equivalent according to recent guidelines. Given the limitations described previously, however, the wisdom of applying this approach to patients with less severe intermediate-risk pulmonary embolism remains unclear and will benefit from additional studies, including those assessing long-term functional outcomes, applying mechanical thrombectomy, and potentially using safer background anticoagulants, such as factor XI or factor XIa inhibitors.”

Reference

  1. Rosenfield K, Klok FA, Piazza G, et al; HI-PEITHO Investigators. Ultrasound-facilitated, catheter-directed fibrinolysis for acute pulmonary embolism. N Engl J Med. Published online March 28, 2026. doi:10.1056/NEJMoa2516567
  2. Spyropoulos AC, Vedantham S. Advanced therapy for intermediate-risk pulmonary embolism. N Engl J Med. Published online March 28, 2026. doi:10.1056/NEJMe2603115