Desmoteplase in acute massive pulmonary thromboembolism.
Alteplase is standard therapy for patients with acute, massive pulmonary embolism. The novel plasminogen activator desmoteplase displays high fibrin specificity and selectivity for fibrinbound plasminogen. In a preclinical model desmoteplase was twice as potent with a shorter lysis time and lower reocclusion rate. We conducted a phase II study comparing 125, 180, and 250 microg/kg bodyweight desmoteplase with 100 mg alteplase. Efficacy criteria were total pulmonary resistance (TPR), mean pulmonary artery pressure (mPAP), and Miller Index. Intention to treat analysis of 34 patients. The reduction of TPR after 24 hours was comparable between desmoteplase 180 microg/kg and alteplase (-48.0 +/- 22.4 vs. -50.4 +/- 16.3%; p = n.s. vs. alteplase; p = 0.0002 and p<0.0001 vs. baseline). The greatest effect was achieved with desmoteplase 250 microg/kg (-56.0 +/- 29.4%; p = n.s. vs. alteplase, p = 0.0055 vs. baseline). Two hours after treatment PAP was reduced by 27.9 (p = 0.0004 vs. baseline) and 30.4% (p = 0.015 vs. baseline) with the higher doses of desmoteplase and 29.6% with alteplase (p = 0.0006 vs. baseline). Further PAP reduction after 6 hours was most pronounced in the desmoteplase 250 microg/kg group (-40.1 +/- 18.0%; p = 0.0028 vs. baseline). The reduction of the Miller Index was greatest using desmoteplase 250 microg/kg (-35.0 +/- 21.7%; p = 0.011 vs. baseline), and alteplase (-41.6 +/- 27.2%; p = 0.0003 vs. baseline). Safety did not differ among the 4 groups. The study results suggest that desmoteplase at doses of 180 and 250 microg/kg had similar or greater efficacy compared to alteplase 100 mg. Onset of action was faster, safety was comparable.
Tebbe
Ulrich
U
Klinikum Lippe GmbH, Fachbereich Herz-Kreislauf, Röntgenstrasse 18, 32756 Detmold, Germany. ulrich.tebbe@klinikum-lippe.de
Bramlage
Peter
P
Graf
Andreas
A
Lechleitner
Peter
P
Bode
Christoph
C
Riess
Friedrich-Christian
FC
Clemens
Norbert
N
Al-Rawi
Yasir
Y
Konstantinides
Stavros
S
Goldhaber
Samuel Z
SZ
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000494:pharmacology / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000188:drug therapy*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects; D055815:Young Adult
D005343:Fibrinolytic Agents; C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D005340:Fibrinogen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator