Catheter-Directed Fibrinolysis Reduces Risks in Intermediate-Risk Pulmonary Embolism: NEJM

The study utilized blinded outcome assessment methodology to ensure that the quality of data collected remained the best possible. Specifically, this study focused on intermediate-risk pulmonary embolism subjects as per the inclusion criteria, which specified that only those patients who had an elevated ratio between their right ventricular and left ventricular end-diastolic diameters (>1.0) and troponin levels (indicating myocardial injury) would be recruited. In addition, they needed to show signs of two or more indicators of cardiorespiratory compromise, such as heart rate (>100/min), respiratory rate (>20/min), or systolic blood pressure (<110 mm Hg). The final number of subjects recruited was 544, with an average age of 58.2 years and a proportion of 42.6% females. They were subsequently randomized to receive either the treatment (n=273) or the placebo (n=271).

Key findings:

• The intervention proved its therapeutic superiority since the number of cases with the primary outcome event was significantly lower among the intervention group participants (n = 11, 4.0%, 95% CI, 2.3 to 7.1) than among those who received placebo (n = 28, 10.3%, 95% CI, 7.2 to 14.5).

• The relative risk for developing a major outcome was 0.39 (95% CI, 0.20 to 0.77; P=0.005).

• One of the most important risks associated with the use of fibrinolytic agents is major bleeding.

• Within the first week after starting the treatment, the incidence of major bleeding was higher among the intervention group patients (n = 11, 4.1%) than among those from the control group (n = 6, 2.2%), but the difference was not statistically significant (P=0.32).

• The incidence of major bleeding did not substantially change during the entire 30-day period (n = 11, 4.1% vs n = 8, 3.0%; P=0.64).

• No cases of intracranial hemorrhage were observed within both groups during the course of the study.

• There were no significant differences between the groups regarding other severe adverse events within the first 30 days after admission.

The findings of this study indicate that ultrasound-assisted catheter-directed thrombolysis with anticoagulation is a more superior therapeutic strategy compared to the standard regimen of anticoagulation alone. It decreases the occurrence of cardio-respiratory failure and reoccurrence of symptoms during the first week by a significant amount, thus providing a safer way to recover from the condition than through anticoagulation alone. The safety aspect, including no incidence of intracranial bleeding, also makes catheter-directed methods a more suitable choice for treatment when a patient shows high-risk factors.

Reference:

Rosenfield, K., Klok, F. A., Piazza, G., Sharp, A. S. P., Ní Áinle, F., Jaff, M. R., Barco, S., Goldhaber, S. Z., Kucher, N., Lang, I. M., Schmidtmann, I., Sterling, K. M., Araszkiewicz, A., Arora, V., Cires-Drouet, R., Coghlan, J., Hobohm, L., Ito, W. D., Jacobson, K., Kaiser, C., … HI-PEITHO Investigators (2026). Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism. The New England journal of medicine, 10.1056/NEJMoa2516567. Advance online publication. https://doi.org/10.1056/NEJMoa2516567