title: Dose-ranging study with a new two-chain rt-PA in patients with acute myocardial infarction: a multicenter trial.
abstract: Tissue-type plasminogen activator (t-PA) derived from a melanoma cell line was first used in patients with acute myocardial infarction in the early 1980s. Recombinant DNA technology then allowed production of large amounts of t-PA. The TIMI-I trial used a two-chain recombinant (rt-PA) product. A predominantly single-chain rt-PA (alteplase) was used in the majority of the TIMI II trial. The present study used a different form of two-chain rt-PA (duteplase) to determine the effective dose for thrombolysis at 60 min, and to evaluate time to reperfusion, reocclusion at 72-96 h, coagulation profiles, and bleeding events. Duteplase was given intravenously to 75 patients a mean of 3.8 +/- 1 h after the onset of myocardial infarction. Following angiography demonstrating coronary occlusion, 23 patients received a low dose of duteplase [0.16-0.29 million international units per kilogram (MIU/kg)] over 60 min followed by a 5-h infusion in conjunction with heparin, 25 patients received a middle dose (0.30-0.41 MIU/kg) and 23 patients received a high dose (0.43-0.74 MIU/kg). Angiography was then performed every 15 min x 4. Progressive recanalization occurred over 60 min (median 45 min) with an overall success rate of 59% (mean 60-min dose: 0.37 MIU/kg). No dose-response relationship was observed. The reocclusion rate was 9% at 72-96 h. Reductions in fibrinogen and plasminogen correlated with dose, but clinical events did not.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Cardiovascular Research Division, Deaconess and Sacred Heart Medical Centers, Spokane, Washington.
authors.forename: M A
authors.initials: MA
authors.lastname: DeWood
authors.forename: P B
authors.initials: PB
authors.lastname: Kurnik
authors.forename: M K
authors.initials: MK
authors.lastname: Jolly
authors.forename: A C
authors.initials: AC
authors.lastname: Jain
authors.forename: F
authors.initials: F
authors.lastname: Khaja
authors.forename: H J
authors.initials: HJ
authors.lastname: Gorfinkel
authors.forename: D L
authors.initials: DL
authors.lastname: Morris
authors.forename: L
authors.initials: L
authors.lastname: Satler
authors.forename: J
authors.initials: J
authors.lastname: LittleJohn
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010958:Plasminogen / Q000032:analysis; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014654:Vascular Patency / Q000187:drug effects
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D011994:Recombinant Proteins; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; C068645:duteplase