Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism.
BACKGROUND
In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients.


RESULTS
Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism.


CONCLUSIONS
In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications.


BACKGROUND
http://www.clinicaltrials.gov. Unique identifier: NCT01166997.
Division of Vascular Medicine, Swiss Cardiovascular Center, University Hospital Bern, Bern, Switzerland (N.K., I.B.); Helios Hospital Siegburg, Siegburg, Germany (P.B., J.H., R.M.); Internal Medicine III, University Hospital Heidelberg, Heidelberg, Germany (O.J.M., E.B.); Großhadern Hospital, Ludwig-Maximilians University Munich, Munich, Germany (C.K., M.G., P.L.); University Hospital Carl Gustav Carus of Technical University Dresden, Dresden, Germany (J.B.-W., R.H., S.W.); Dortmund Hospital, Dortmund, Germany (T.H., A.B.); Hospital Lippe-Detmold, Detmold, Germany (U.T., D.H.); and University Hospital of Ernst-Moritz-Arndt University, Greifswald, Germany (H.G., K.E.).
Nils
N
Kucher
Peter
P
Boekstegers
Oliver J
OJ
Müller
Christian
C
Kupatt
Jan
J
Beyer-Westendorf
Thomas
T
Heitzer
Ulrich
U
Tebbe
Jan
J
Horstkotte
Ralf
R
Müller
Erwin
E
Blessing
Martin
M
Greif
Philipp
P
Lange
Ralf-Thorsten
RT
Hoffmann
Sebastian
S
Werth
Achim
A
Barmeyer
Dirk
D
Härtel
Henriette
H
Grünwald
Klaus
K
Empen
Iris
I
Baumgartner
D000208:Acute Disease; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D062666:Vascular Access Devices
D011994:Recombinant Proteins; D006493:Heparin; D010959:Tissue Plasminogen Activator
pulmonary embolism