Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism

J Kjaergaard; L E Bang; E Sonne-Holm; S Wiberg; L Holmvang; J F Lassen; R Sørensen; D E Høfsten; P S Ulriksen; S Jawad; P Palm; C Søe; M K Ersbøll; S Boesgaard; J E Møller; J J Thune; C Hassager; H-H Tilsted; J Lønborg; M Egstrup; O P Kristiansen; E Seven; M G Lindholm; K Eskesen; S Fanø; J Carlsen

doi:10.1093/cvr/cvag038

Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism

J Kjaergaard^*, L E Bang, E Sonne-Holm, S Wiberg, L Holmvang, J F Lassen, R Sørensen, D E Høfsten, P S Ulriksen, S Jawad, P Palm, C Søe, M K Ersbøll, S Boesgaard, J E Møller, J J Thune, C Hassager, H-H Tilsted, J Lønborg, M EgstrupO P Kristiansen, E Seven, M G Lindholm, K Eskesen, S Fanø, J Carlsen

^*Corresponding author for this work

Abstract

AIMS: Intermediate high-risk pulmonary embolism (PE) is associated with increased risk of haemodynamic deterioration and death, but balancing the risk of thrombolytics or catheter-based treatment and efficacy has been challenging. This trial compared the additional efficacy of catheter-based ultrasound low-dose thrombolysis (USAT) over intravenous low-dose thrombolysis or heparin alone.

METHODS AND RESULTS: In an investigator-initiated randomized clinical multicentre trial, we randomized 210 adult patients with acute, intermediate high-risk PE admitted to emergency departments in two regions of Denmark. Patients were allocated 1:1:1 to one of three treatment strata: low-dose thrombolysis (20 mg alteplase administered over 6 h) by USAT, by intravenous administration, or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0-40 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48-96 h post-randomization. Two comparisons were investigated: the reduction of rmMS with low-dose thrombolysis (USAT or intravenously) compared to heparin alone and the reduction of rmMS with low-dose thrombolysis administered by USAT compared to the intravenous route. The safety endpoint included the risk of bleeding.We included 210 patients with acute PE, 49% were female, the mean age was 70 (IQR 62-76), and the mean body mass index was 30 (26-34). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points (95% CI 2.2-5.0, P < 0.001), but the reduction in rmMS was not different in the ultrasound-assisted thrombolysis (USAT) vs. the intravenous route, mean difference -0.1 (95% CI: -1.9-1.7), P = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statistically significant. No differences in other outcomes were observed.

CONCLUSION: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk PE. However, USAT did not show greater thrombus reduction than intravenous thrombolysis. The rate of death and risk of bleeding complications were increased with low-dose thrombolysis.

TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.

Original language	English
Journal	Cardiovascular Research
Volume	122
Issue number	4
Pages (from-to)	539-549
Number of pages	11
ISSN	0008-6363
DOIs	https://doi.org/10.1093/cvr/cvag038
Publication status	Published - 26 Mar 2026

Keywords

Catheter-based thrombolysis
Pulmonary embolism
Thrombolysis
Venous thromboembolism

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10.1093/cvr/cvag038

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Kjaergaard, J., Bang, L. E., Sonne-Holm, E., Wiberg, S., Holmvang, L., Lassen, J. F., Sørensen, R., Høfsten, D. E., Ulriksen, P. S., Jawad, S., Palm, P., Søe, C., Ersbøll, M. K., Boesgaard, S., Møller, J. E., Thune, J. J., Hassager, C., Tilsted, H.-H., Lønborg, J., ... Carlsen, J. (2026). Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism. Cardiovascular Research, 122(4), 539-549. https://doi.org/10.1093/cvr/cvag038

Kjaergaard, J , Bang, LE , Sonne-Holm, E , Wiberg, S , Holmvang, L, Lassen, JF, Sørensen, R, Høfsten, DE, Ulriksen, PS, Jawad, S, Palm, P, Søe, C, Ersbøll, MK , Boesgaard, S , Møller, JE , Thune, JJ , Hassager, C , Tilsted, H-H , Lønborg, J, Egstrup, M, Kristiansen, OP , Seven, E, Lindholm, MG, Eskesen, K, Fanø, S & Carlsen, J 2026, 'Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism', Cardiovascular Research, vol. 122, no. 4, pp. 539-549. https://doi.org/10.1093/cvr/cvag038

@article{e97b51d61dd840f0842e8a3de5edc264,

title = "Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism",

abstract = "AIMS: Intermediate high-risk pulmonary embolism (PE) is associated with increased risk of haemodynamic deterioration and death, but balancing the risk of thrombolytics or catheter-based treatment and efficacy has been challenging. This trial compared the additional efficacy of catheter-based ultrasound low-dose thrombolysis (USAT) over intravenous low-dose thrombolysis or heparin alone.METHODS AND RESULTS: In an investigator-initiated randomized clinical multicentre trial, we randomized 210 adult patients with acute, intermediate high-risk PE admitted to emergency departments in two regions of Denmark. Patients were allocated 1:1:1 to one of three treatment strata: low-dose thrombolysis (20 mg alteplase administered over 6 h) by USAT, by intravenous administration, or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0-40 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48-96 h post-randomization. Two comparisons were investigated: the reduction of rmMS with low-dose thrombolysis (USAT or intravenously) compared to heparin alone and the reduction of rmMS with low-dose thrombolysis administered by USAT compared to the intravenous route. The safety endpoint included the risk of bleeding.We included 210 patients with acute PE, 49\% were female, the mean age was 70 (IQR 62-76), and the mean body mass index was 30 (26-34). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points (95\% CI 2.2-5.0, P < 0.001), but the reduction in rmMS was not different in the ultrasound-assisted thrombolysis (USAT) vs. the intravenous route, mean difference -0.1 (95\% CI: -1.9-1.7), P = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statistically significant. No differences in other outcomes were observed.CONCLUSION: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk PE. However, USAT did not show greater thrombus reduction than intravenous thrombolysis. The rate of death and risk of bleeding complications were increased with low-dose thrombolysis.TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.",

keywords = "Catheter-based thrombolysis, Pulmonary embolism, Thrombolysis, Venous thromboembolism",

author = "J Kjaergaard and Bang, \{L E\} and E Sonne-Holm and S Wiberg and L Holmvang and Lassen, \{J F\} and R S{\o}rensen and H{\o}fsten, \{D E\} and Ulriksen, \{P S\} and S Jawad and P Palm and C S{\o}e and Ersb{\o}ll, \{M K\} and S Boesgaard and M{\o}ller, \{J E\} and Thune, \{J J\} and C Hassager and H-H Tilsted and J L{\o}nborg and M Egstrup and Kristiansen, \{O P\} and E Seven and Lindholm, \{M G\} and K Eskesen and S Fan{\o} and J Carlsen",

note = "{\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].",

year = "2026",

month = mar,

day = "26",

doi = "10.1093/cvr/cvag038",

language = "English",

volume = "122",

pages = "539--549",

journal = "Cardiovascular Research",

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publisher = "Oxford University Press",

number = "4",

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TY - JOUR

T1 - Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism

AU - Kjaergaard, J

AU - Bang, L E

AU - Sonne-Holm, E

AU - Wiberg, S

AU - Holmvang, L

AU - Lassen, J F

AU - Sørensen, R

AU - Høfsten, D E

AU - Ulriksen, P S

AU - Jawad, S

AU - Palm, P

AU - Søe, C

AU - Ersbøll, M K

AU - Boesgaard, S

AU - Møller, J E

AU - Thune, J J

AU - Hassager, C

AU - Tilsted, H-H

AU - Lønborg, J

AU - Egstrup, M

AU - Kristiansen, O P

AU - Seven, E

AU - Lindholm, M G

AU - Eskesen, K

AU - Fanø, S

AU - Carlsen, J

N1 - © The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

PY - 2026/3/26

Y1 - 2026/3/26

N2 - AIMS: Intermediate high-risk pulmonary embolism (PE) is associated with increased risk of haemodynamic deterioration and death, but balancing the risk of thrombolytics or catheter-based treatment and efficacy has been challenging. This trial compared the additional efficacy of catheter-based ultrasound low-dose thrombolysis (USAT) over intravenous low-dose thrombolysis or heparin alone.METHODS AND RESULTS: In an investigator-initiated randomized clinical multicentre trial, we randomized 210 adult patients with acute, intermediate high-risk PE admitted to emergency departments in two regions of Denmark. Patients were allocated 1:1:1 to one of three treatment strata: low-dose thrombolysis (20 mg alteplase administered over 6 h) by USAT, by intravenous administration, or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0-40 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48-96 h post-randomization. Two comparisons were investigated: the reduction of rmMS with low-dose thrombolysis (USAT or intravenously) compared to heparin alone and the reduction of rmMS with low-dose thrombolysis administered by USAT compared to the intravenous route. The safety endpoint included the risk of bleeding.We included 210 patients with acute PE, 49% were female, the mean age was 70 (IQR 62-76), and the mean body mass index was 30 (26-34). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points (95% CI 2.2-5.0, P < 0.001), but the reduction in rmMS was not different in the ultrasound-assisted thrombolysis (USAT) vs. the intravenous route, mean difference -0.1 (95% CI: -1.9-1.7), P = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statistically significant. No differences in other outcomes were observed.CONCLUSION: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk PE. However, USAT did not show greater thrombus reduction than intravenous thrombolysis. The rate of death and risk of bleeding complications were increased with low-dose thrombolysis.TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.

AB - AIMS: Intermediate high-risk pulmonary embolism (PE) is associated with increased risk of haemodynamic deterioration and death, but balancing the risk of thrombolytics or catheter-based treatment and efficacy has been challenging. This trial compared the additional efficacy of catheter-based ultrasound low-dose thrombolysis (USAT) over intravenous low-dose thrombolysis or heparin alone.METHODS AND RESULTS: In an investigator-initiated randomized clinical multicentre trial, we randomized 210 adult patients with acute, intermediate high-risk PE admitted to emergency departments in two regions of Denmark. Patients were allocated 1:1:1 to one of three treatment strata: low-dose thrombolysis (20 mg alteplase administered over 6 h) by USAT, by intravenous administration, or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0-40 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48-96 h post-randomization. Two comparisons were investigated: the reduction of rmMS with low-dose thrombolysis (USAT or intravenously) compared to heparin alone and the reduction of rmMS with low-dose thrombolysis administered by USAT compared to the intravenous route. The safety endpoint included the risk of bleeding.We included 210 patients with acute PE, 49% were female, the mean age was 70 (IQR 62-76), and the mean body mass index was 30 (26-34). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points (95% CI 2.2-5.0, P < 0.001), but the reduction in rmMS was not different in the ultrasound-assisted thrombolysis (USAT) vs. the intravenous route, mean difference -0.1 (95% CI: -1.9-1.7), P = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statistically significant. No differences in other outcomes were observed.CONCLUSION: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk PE. However, USAT did not show greater thrombus reduction than intravenous thrombolysis. The rate of death and risk of bleeding complications were increased with low-dose thrombolysis.TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.

KW - Catheter-based thrombolysis

KW - Pulmonary embolism

KW - Thrombolysis

KW - Venous thromboembolism

U2 - 10.1093/cvr/cvag038

DO - 10.1093/cvr/cvag038

M3 - Journal article

C2 - 41610160

SN - 0008-6363

VL - 122

SP - 539

EP - 549

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 4

ER -

Randomized trial of low-dose -, ultrasound assisted thrombolysis or heparin for pulmonary embolism

Abstract

Keywords

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