Effectiveness and safety of half-dose thrombolysis in intermediate-high risk pulmonary embolism: a single centre experience
Authors: Picariello C , Zagarese G , Santori V , Marcantoni L , Maddalozzo A , Giordan M , Ribichini F , Zanon F 
Published: May 2024

Abstract

Funding Acknowledgements
None.

Introduction
According to current guidelines, full-dose systemic thrombolysis for pulmonary embolism (PE) is limited to patients either classified as high risk or presenting intermediate risk with hemodynamically instability. As evidenced by recent clinical trials, "low" half-dose (50 mg) tissue plasminogen activator (HDrtPA) appears to offer a safe, effective alternative with a low bleeding risk, especially if catheter directed therapies are not available.

Purpose
we aimed to evaluate if HDrtPA in intermediate-high risk PE could improve right ventricular (RV)-arterial coupling by means of TAPSE/PAPs ratio, right ventricular basal dimensions in 4 chambers (RVD1), and tricuspid velocity (TV) between admission and discharge, exploring eventual associated bleeding risk.

Methods
we retrospectively analized 90 intermediate-high risk PE patients consecutively admitted to our intensive cardiac care unit between January 2016 and May 2023. Diagnosis was achieved by computed tomography in all cases. All patients underwent echocardiographic assessment upon admission and at discharge along with baseline lab values.
HDrtPA patients (Group A, n=28) received low-dose thrombolytic therapy (0,6 mg/kg maximum 50 mg in 1 hour) combined with unfractionated heparin. Standard anticoagulation patients (Group B) included patients exclusively treated with parenteral anticoagulants. Primary endpoint was echocardiographic improvement of RV-arterial coupling (TAPSE/PAPS), and of pulmonary pressures (tricuspid velocity, TV) and right ventricular basal dimension (RVD1) between admission and dis-charge in the two treatment arms. To perform this analysis, linear regression models with Inverse Probability Weighting (IPW) propensity scores were used. Secondary endpoint was presence of mayor or minor bleeding between groups, and a descriptive analysis of mortality due to paucity of events.

Results
in the whole population mean age was 73.48 ± 12.49 (mean ± sd) and n=43 (47.8%) were males. Between admission and discharge, group A (HDrtPA) had an improvement of TAPSE/PAPs (+0.16, p=0.05, CI 95%: -0.002; 0.325), of RVD1 (-6.00 mm, p &lt;0.01, CI 95%: -2.59; 9.41). Reduction of TV values (-0.45 m/s, p=0.108, CI 95%: -1.02; 0.10) was not statistically significant at IPW propensity score, but deserves further investigations. No significant increase of major bleedings were recorded between two groups (Group A: 1/28 3.5%, Group B: 0/52 0%) with an acceptable number of minor, non fatal bleedings (Group A: 7/28: 25%, Group B 1/62 1.6%). Death occurred in 3 patients in group A (10%) and 1 patient in group B (1.6%).

Conclusion
half dose of tissue plasminogen activator (HDrtPA) offer a promising alternative to anticoagulation alone therapy in selected patients with high-intermediate risk pulmonary embolism. In our experience, this approach seems to acutely improve RV-arterial coupling and right ventricular dimensions, without an increase of major bleeding risk.