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 af dette arbejde

Abstract

AIMS: Intermediate high-risk pulmonary embolism is associated with increased risk of hemodynamic deterioration and death, but balancing 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 multi-center trial we randomized 210 adult patients with acute, intermediate high-risk pulmonary embolism 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 hours) 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 intravenous route. Safety endpoint included risk of bleeding.We included 210 patients with acute pulmonary embolism, 49% were female, mean age was 70 (IQR 62-76) and mean body mass index 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 vs. 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 statically significant. No differences in other outcomes were observed.

CONCLUSIONS: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk pulmonary embolism. However, ultrasound assisted thrombolysis did not show greater thrombus reduction than thrombolysis administrated intravenously. The rate of death and risk of bleeding complications was increased with low-dose thrombolysis.

TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.

Originalsprog	Engelsk
Tidsskrift	Cardiovascular Research
ISSN	0008-6363
DOI	https://doi.org/10.1093/cvr/cvag038
Status	E-pub ahead of print - 29 jan. 2026

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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. Advance online publication. 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. 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 is associated with increased risk of hemodynamic deterioration and death, but balancing 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 multi-center trial we randomized 210 adult patients with acute, intermediate high-risk pulmonary embolism 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 hours) 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 intravenous route. Safety endpoint included risk of bleeding.We included 210 patients with acute pulmonary embolism, 49\% were female, mean age was 70 (IQR 62-76) and mean body mass index 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 vs. 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 statically significant. No differences in other outcomes were observed.CONCLUSIONS: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk pulmonary embolism. However, ultrasound assisted thrombolysis did not show greater thrombus reduction than thrombolysis administrated intravenously. The rate of death and risk of bleeding complications was increased with low-dose thrombolysis.TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.",

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 = jan,

day = "29",

doi = "10.1093/cvr/cvag038",

language = "English",

journal = "Cardiovascular Research",

issn = "0008-6363",

publisher = "Oxford University Press",

}

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 - 2026/1/29

Y1 - 2026/1/29

N2 - AIMS: Intermediate high-risk pulmonary embolism is associated with increased risk of hemodynamic deterioration and death, but balancing 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 multi-center trial we randomized 210 adult patients with acute, intermediate high-risk pulmonary embolism 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 hours) 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 intravenous route. Safety endpoint included risk of bleeding.We included 210 patients with acute pulmonary embolism, 49% were female, mean age was 70 (IQR 62-76) and mean body mass index 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 vs. 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 statically significant. No differences in other outcomes were observed.CONCLUSIONS: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk pulmonary embolism. However, ultrasound assisted thrombolysis did not show greater thrombus reduction than thrombolysis administrated intravenously. The rate of death and risk of bleeding complications was increased with low-dose thrombolysis.TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.

AB - AIMS: Intermediate high-risk pulmonary embolism is associated with increased risk of hemodynamic deterioration and death, but balancing 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 multi-center trial we randomized 210 adult patients with acute, intermediate high-risk pulmonary embolism 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 hours) 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 intravenous route. Safety endpoint included risk of bleeding.We included 210 patients with acute pulmonary embolism, 49% were female, mean age was 70 (IQR 62-76) and mean body mass index 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 vs. 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 statically significant. No differences in other outcomes were observed.CONCLUSIONS: Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk pulmonary embolism. However, ultrasound assisted thrombolysis did not show greater thrombus reduction than thrombolysis administrated intravenously. The rate of death and risk of bleeding complications was increased with low-dose thrombolysis.TRIAL REGISTRATION: clinicaltrials.gov, NCT04088292.

U2 - 10.1093/cvr/cvag038

DO - 10.1093/cvr/cvag038

M3 - Journal article

C2 - 41610160

SN - 0008-6363

JO - Cardiovascular Research

JF - Cardiovascular Research

ER -

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

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