Key result
Ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation reduces 7-day major PE events versus anticoagulation alone.
Why the trial?
The trial was conducted to evaluate whether ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation reduces the risk of pulmonary embolism-related adverse events compared to anticoagulation alone in patients with acute, intermediate-risk pulmonary embolism.
Does ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation reduce the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days in patients with acute, intermediate-risk pulmonary embolism?
RCT
Does ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation reduce the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days in patients with acute, intermediate-risk pulmonary embolism?
In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation reduces the short-term risk of adverse clinical outcomes compared to anticoagulation alone.
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Experts broadly read HI-PEITHO as practice-changing for high-intermediate-risk PE, though some caution against over-extrapolating the benefit to lower-risk patients and note that individual endpoints like death and functional status did not separate.
Most experts view this as the first rigorous evidence that catheter-directed fibrinolysis improves outcomes in a carefully selected intermediate-risk PE population, filling a long-standing evidence gap. Enthusiasm is tempered by questions about whether the composite benefit translates to harder individual endpoints and whether the findings should be applied beyond the trial's strict enrollment criteria. The live question is how broadly clinicians and guidelines should extend these results.
Multiple experts agree that HI-PEITHO fills a critical evidence gap and that catheter-directed fibrinolysis benefits the right patients at acceptable bleeding risk, but caution that results should not be extrapolated to broader intermediate-risk populations.
Practice-changing result vs. marginal clinical significance
Whether these findings should influence management of patients with less severe intermediate-risk PE remains an open question flagged by multiple experts. Individual endpoints such as mortality, recurrent PE, and 6-minute walk distance did not significantly differ, leaving uncertainty about the depth of clinical benefit. How quickly guidelines will incorporate catheter-directed fibrinolysis as a recommended option for this population is unresolved.
Westafer notes there was no significant difference in death, recurrent PE, or 6-minute walk at 30 days. She argues that health systems and clinicians must weigh increased resource utilization, including procedural cost and ICU admissions, against a benefit that may be of marginal clinical significance.
Barnes says the study largely confirms that catheter-based thrombolysis improves outcomes but warns clinicians against extrapolating these findings to a much broader set of patients.
Beckman notes there was no understanding before this trial of how to manage patients in the high-intermediate zone. He sees the result as showing that catheter-directed thrombolysis applied up front in the appropriate patients certainly derived benefit.
Supports CDT in intermediate-risk PE with distress; extends prior imaging data to clinical outcomes.
BACKGROUND: Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. METHODS: We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of ≥1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of ≤110 mm Hg, a heart rate of ≥100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. RESULTS: The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) age was 58.2±13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = 0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P = 0.32); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred. CONCLUSIONS: In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).
Rosenfield et al. (2026) conducted an RCT in Acute, intermediate-risk pulmonary embolism. Ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation vs. Anticoagulation alone was evaluated on Composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. Ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower 7-day risk of PE-related death, decompensation, or recurrence than anticoagulation alone.
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