Low-dose, short-duration catheter-directed thrombolysis for acute intermediate-high-risk pulmonary embolism: the BETULA trial.

Abstract

Background: Catheter-directed thrombolysis (CDT) reduces the right-to-left ventricular ratio (RV/LV ratio) in patients with intermediate-risk pulmonary embolism (PE). Prior randomised studies comparing CDT to anticoagulation used ultrasound-assisted devices and high doses of thrombolytics with extended infusion durations, which may increase healthcare costs and complications, thereby limiting its clinical applicability.

Aims: We sought to evaluate the efficacy and safety of low-dose, short-duration CDT compared with unfractionated heparin (UFH) in patients with acute intermediate-high-risk PE.

Methods: In this open-label, randomised controlled trial, patients with acute intermediate-high-risk PE were randomised 1:1 to receive CDT (4 mg recombinant tissue plasminogen activator [r-tPA] per catheter over 2 hours) plus UFH or UFH alone. The primary endpoint was the change in RV/LV ratio at 24 hours. Secondary endpoints included thrombus burden reduction, changes in vital signs and echocardiographic measures of RV function, length of hospital stay, 30-day mortality, and 90-day recurrent PE. Safety endpoints included major and minor bleeding.

Results: Between August 2020 and October 2024, 60 patients were randomised, with 58 completing follow-up (CDT: n=29; UFH: n=29). CDT plus UFH improved the RV/LV ratio at 24 hours compared with UFH alone (-0.17 vs +0.02; p=0.01). Secondary endpoints did not differ between groups. One death occurred in the UFH group. One patient experienced haemodynamic deterioration during CDT, successfully managed with additional r-tPA. No major bleeding occurred. Minor bleeding occurred in three patients (10%) in the CDT group and one (3%) in the UFH group (p=0.29).

Conclusions: Low-dose, short-duration CDT plus UFH improved the RV/LV ratio without increasing major bleeding compared with UFH alone in intermediate-high-risk PE.