{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:51:00Z","timestamp":1793947860956,"version":"4.8.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004046","name":"Karen Elise Jensen foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008218","name":"Gangsted foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008218","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rigshospitalets Research foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>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\u2005mg alteplase administered over 6\u2005h) by USAT, by intravenous administration, or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0\u201340 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48\u201396\u2005h 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.<\/jats:p>\n                    <jats:p>We included 210 patients with acute PE, 49% were female, the mean age was 70 (IQR 62\u201376), and the mean body mass index was 30 (26\u201334). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points (95% CI 2.2\u20135.0, P &amp;lt; 0.001), but the reduction in rmMS was not different in the ultrasound-assisted thrombolysis (USAT) vs. the intravenous route, mean difference \u22120.1 (95% CI: \u22121.9\u20131.7), P = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statistically significant. No differences in other outcomes were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>clinicaltrials.gov, NCT04088292.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag038","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:38:02Z","timestamp":1769603882000},"page":"539-549","source":"Crossref","is-referenced-by-count":18,"title":["Randomized trial of low-dose, ultrasound-assisted thrombolysis or heparin for pulmonary embolism"],"prefix":"10.1093","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5244-0399","authenticated-orcid":false,"given":"Jesper","family":"Kjaergaard","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia E","family":"Bang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Sonne-Holm","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-7189","authenticated-orcid":false,"given":"Sebastian","family":"Wiberg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-378X","authenticated-orcid":false,"given":"Lene","family":"Holmvang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Flensted","family":"Lassen","sequence":"additional","affiliation":[{"name":"Department of Cardiology B, Odense University Hospital , J. 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Winsl\u00f8ws Vej 4, DK5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9238-6681","authenticated-orcid":false,"given":"Rikke","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Den Eik","family":"H\u00f8fsten","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Sommer","family":"Ulriksen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]},{"name":"Department of Radiology, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Jawad","sequence":"additional","affiliation":[{"name":"Department of Radiology, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8437-5445","authenticated-orcid":false,"given":"Pernille","family":"Palm","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conni","family":"S\u00f8e","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads K","family":"Ersb\u00f8ll","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Boesgaard","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob E","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Cardiology B, Odense University Hospital , J. 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Winsl\u00f8ws Vej 4, DK5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Jakob","family":"Thune","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 Copenhagen ,","place":["Denmark"]},{"name":"Department of Cardiology, Copenhagen University Hospital Bispebjerg and Frederiksberg , Bispebjerg Bakke 23, DK2400 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1199-0981","authenticated-orcid":false,"given":"Christian","family":"Hassager","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Heart Center, Copenhagen University Hospital Rigshospitalet , Blegdamsvej 9, DK2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health Science, University of Copenhagen , Blegdamsvej 3B, DK2200 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