New recombinant glycosylated prourokinase for treatment of patients with acute myocardial infarction. Prourokinase Study Group.
OBJECTIVE
Three dosage regimens of a new recombinant glycosylated prourokinase (A-74187) were evaluated by measuring coronary artery patency at 90 min in patients with acute myocardial infarction.


BACKGROUND
Prourokinase is a thrombolytic drug with unique pharmacologic properties that may be clinically advantageous.


METHODS
Aspirin (325 mg), intravenous heparin and prourokinase (60- or 80-mg monotherapy or 60 mg "primed" with a preceding bolus dose of 250,000 IU of recombinant urokinase) were administered to 128 patients. Coronary angiography was performed at 60 min (wherever possible), 90 min (primary end point) and 24 h to determine arterial patency and reocclusion rates. Plasma was collected serially to measure fibrinogen, plasminogen, thrombin antithrombin III and fibrinopeptide A. Clinical events until hospital discharge were recorded.


RESULTS
The coronary artery patency rate at 90 min was similar for all three regimens, averaging 73% (95% confidence interval [CI] 64% to 80%); Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow rates averaged 52% (95% CI 42% to 61%). Arterial patency at 60 min was 62% (95% CI 50% to 73%), and reocclusion occurred in 1.4% (95% CI 0.1% to 4.1%). Prourokinase demonstrated relative fibrin specificity at all doses studied. Fibrinopeptide A and thrombin antithrombin III levels were elevated at baseline and declined rapidly during the 1st 12 h. There was no difference in the baseline values of these thrombin markers between patients with patent versus closed arteries at 90 min. There was one death; no strokes occurred.


CONCLUSIONS
A-74187 prourokinase is a rapid-acting, effective fibrin-specific thrombolytic agent. Reocclusion was unusual, possibly because of aggressive anticoagulation with intravenous heparin or unique features of the drug. Full definition of the clinical effectiveness of this drug merits examination in future randomized trials evaluating clinical and angiographic effectiveness.
Weaver
W D
WD
Myocardial Infarction Triage and Intervention (MITI) Project Group, University of Washington, Seattle.
Hartmann
J R
JR
Anderson
J L
JL
Reddy
P S
PS
Sobolski
J C
JC
Sasahara
A A
AA
D001241:Aspirin / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
D004792:Enzyme Precursors; D011994:Recombinant Proteins; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator; D001241:Aspirin; C067551:saruplase