title: A randomized dose-ranging study of rt-PA in acute myocardial infarction. Effects on coronary patency and fibrinolytic parameters.
abstract: This study was designed to examine the relationships between dose of Wellcome two-chain recombinant tissue type-plasminogen activator (BW rt-PA) and coronary patency and fibrinolytic parameters in acute myocardial infarction (AMI). In an open randomized study, patients with AMI (determined by ECG) and symptoms of less than 4 h duration without contraindications for fibrinolytic therapy were treated with rt-PA in nominal doses of 20 (7.7 MU), 50 (14.8-29.6 MU) or 100 mg (29.6-48.2 MU) administered over 90 min followed by intravenous heparin. Coronary patency was determined by coronary arteriography of the infarct-related artery and haematological parameters (fibrinogen, plasminogen, alpha 2-antiplasmin and fibrin(ogen) degradation products) measured at 90 min. Coronary patency increased in a dose-related manner to 53% (95% C.I. 37-69%) in the 100 mg/90 min group. Logistic regression demonstrated a relationship between dose (in MU kg-1) and coronary patency. Fibrinogen at 90 m was reduced to 74 (61.5-86.4%) of the pooled plasma standard in the nominal 100 mg group. Patients with a higher predose fibrinogen had higher reductions of fibrinogen. Serious bleeding occurred in three (3%) patients, and no intracranial bleeds were reported. BW rt-PA produces dose-related patency of the coronary arteries with moderate, dose-related reduction in fibrinogen.
authors.affiliation: Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: R W
authors.initials: RW
authors.lastname: Koster
authors.forename: R
authors.initials: R
authors.lastname: van Stralen
authors.forename: A J
authors.initials: AJ
authors.lastname: McNeill
authors.forename: A A
authors.initials: AA
authors.lastname: Adgey
authors.forename: K A
authors.initials: KA
authors.lastname: Fox
authors.forename: D
authors.initials: D
authors.lastname: Dymond
authors.forename: C
authors.initials: C
authors.lastname: Sponzilli
authors.forename: D
authors.initials: D
authors.lastname: Jewitt
authors.forename: C
authors.initials: C
authors.lastname: Bucknall
authors.forename: C
authors.initials: C
authors.lastname: Kluft
mesh_terms: D000368:Aged; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D014654:Vascular Patency / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator