Catheter-Directed Fibrinolysis Reduces Risks in Intermediate-Risk Pulmonary Embolism: NEJM
A multi-national, adaptive design study was done to assess the benefits associated with the combination of catheter-directed fibrinolysis along with anticoagulation in comparison with the standard care option that is anticoagulation alone. It was concluded that in cases of patients with acute intermediate-risk PE, combining catheter-directed fibrinolysis and anticoagulation results in an improved risk profile with respect to composite end points such as PE-associated death, cardio-respiratory arrest, and recurrence symptoms within seven days in comparison with isolated use of anticoagulation. The study was published in The New England Journal of Medicine by Kenneth R. and colleagues.
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
