title: Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase.
abstract: The recent establishment of a firm therapeutic role for reperfusion in acute myocardial infarction has stimulated interest in the development of more ideal thrombolytic agents. Anisoylated plasminogen streptokinase activator complex (APSAC) is a new plasminogen activator possessing properties that are promising for intravenous thrombolytic application in acute myocardial infarction. To assess the reperfusion potential of intravenous APSAC, a multi-center, angiographically controlled reperfusion trial was performed. An approved thrombolytic regimen of intracoronary streptokinase served as a control. Consenting patients with clinical and electrocardiographic signs of acute myocardial infarction were studied angiographically and 240 qualifying patients with documented coronary occlusion (flow grade 0 or 1) were randomized to treatment in less than 6 h of symptom onset (mean 3.4 h, range 0.4 to 6.0) with either intravenous APSAC (30 U in 2 to 4 min) or intracoronary streptokinase (160,000 U over 60 min). Both groups also received heparin for greater than or equal to 24 h. Reperfusion was evaluated angiographically over 90 min and success was defined as advancement of grade 0 or 1 to grade 2 or 3 flow. Rates of reperfusion for the two treatment regimens were 51% (59 of 115) at 90 min after intravenous APSAC and 60% (67 of 111) after 60 min of intracoronary streptokinase (p less than or equal to 0.18). Reperfusion at any time within the 90 min was observed in 55 and 64%, respectively (p less than or equal to 0.16). Time to reperfusion occurred at 43 +/- 23 min after intravenous and 31 +/- 17 min after intracoronary therapy. The success of intravenous therapy was dependent on the time to treatment: 60% of APSAC patients treated within 4 h exhibited reperfusion compared with 33% of those treated after 4 h (p less than or equal to 0.01). Reperfusion rates were also dependent on initial flow grade (p less than or equal to 0.0001): 48% (81 of 168) for grade 0 (APSAC = 43%, streptokinase = 54%), but 78% for grade 1 (APSAC = 78%, streptokinase = 77%). APSAC given as a rapid injection was generally well tolerated, although the median change in blood pressure at 2 to 4 min was greater after APSAC than after streptokinase (-10 versus -5 mm Hg). Mean plasma fibrogen levels fell more at 90 min after the sixfold higher dose of APSAC than after streptokinase (to 32 versus 64% of control). Reported bleeding events were more frequent after APSAC but occurred primarily at the site of catheter insertion and no event was intracranial.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: University of Utah, LDS Hospital, Division of Cardiology, Salt Lake City 84143.
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: R L
authors.initials: RL
authors.lastname: Rothbard
authors.forename: R A
authors.initials: RA
authors.lastname: Hackworthy
authors.forename: S G
authors.initials: SG
authors.lastname: Sorensen
authors.forename: P G
authors.initials: PG
authors.lastname: Fitzpatrick
authors.forename: C F
authors.initials: CF
authors.lastname: Dahl
authors.forename: A D
authors.initials: AD
authors.lastname: Hagan
authors.forename: K F
authors.initials: KF
authors.lastname: Browne
authors.forename: G P
authors.initials: GP
authors.lastname: Symkoviak
authors.forename: R L
authors.initials: RL
authors.lastname: Menlove
mesh_terms: D000328:Adult; D000368:Aged; D016255:Anistreplase; D001777:Blood Coagulation / Q000187:drug effects; D002986:Clinical Trials as Topic; D003326:Coronary Circulation; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D010958:Plasminogen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011897:Random Allocation; D012008:Recurrence; D013300:Streptokinase / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014654:Vascular Patency
chemical_list: D005343:Fibrinolytic Agents; D016255:Anistreplase; D010958:Plasminogen; D013300:Streptokinase