title: Clot-selective coronary thrombolysis with low-dose synergistic combinations of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator. The Pro-Urokinase for Myocardial Infarction Study Group.
abstract: The effect of simultaneous infusions of low-dose recombinant tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, pro-urokinase) on coronary arterial thrombolysis was investigated in 23 patients treated within 6 hours (mean 2.6 +/- 1.1, range 1.2 to 5.9) of symptoms of an acute myocardial infarction. Infarct artery patency at 90 minutes was achieved in 16 (70%, 95% confidence limits of 0.47 to 0.87) of 23 patients after a 1-hour intravenous infusion of 20 and 16.3 mg of t-PA and scu-PA, respectively. At 90 minutes, the fibrinogen concentration decreased from 369 +/- 207 to 316 +/- 192 mg/dl (p = not significant), while plasminogen decreased to 69 +/- 24% (p = 0.001) and alpha-2-antiplasmin to 77 +/- 24% (p = 0.001) of pretreatment values. Although no bleeding requiring termination of drug infusion or transfusion occurred, 1 patient with cerebrovascular amyloidosis had a fatal intracerebral hemorrhage. These findings suggest that combination therapy may allow substantial reductions in total thrombolytic doses while still achieving effective fibrin-specific coronary thrombolysis.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: J M
authors.initials: JM
authors.lastname: Kirshenbaum
authors.forename: R D
authors.initials: RD
authors.lastname: Bahr
authors.forename: J T
authors.initials: JT
authors.lastname: Flaherty
authors.forename: V
authors.initials: V
authors.lastname: Gurewich
authors.forename: H J
authors.initials: HJ
authors.lastname: Levine
authors.forename: J
authors.initials: J
authors.lastname: Loscalzo
authors.forename: R R
authors.initials: RR
authors.lastname: Schumacher
authors.forename: E J
authors.initials: EJ
authors.lastname: Topol
authors.forename: D W
authors.initials: DW
authors.lastname: Wahr
authors.forename: E
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000328:Adult; D000368:Aged; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000188:drug therapy / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D011994:Recombinant Proteins; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D004338:Drug Combinations; D005338:Fibrin Fibrinogen Degradation Products; D011994:Recombinant Proteins; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator