Pharmacokinetics, thrombolytic efficacy and hemorrhagic risk of different streptokinase regimens in heparin-treated acute myocardial infarction.
The systemic activator activity of 4 streptokinase (SK) regimens (250,000 IU intracoronary, group A; 500,000 IU, group B; 1.5 X 10(6) IU, group C; and 30 U anisoylated plasminogen streptokinase activator complex (APSAC) intravenously, group D) was tested with the fibrin plate technique. One hour after initiation of treatment, the activator activity was highest after APSAC (3.6 +/- 0.9 U), slightly but not significantly less after SK 1.5 X 10(6) IU (3.0 +/- 0.7), and significantly less after SK 500,000 IU (1.6 +/- 0.5) and 250,000 IU (0.6 +/- 0.5), p less than 0.001. After SK, activator activity half-lives were 184 minutes (group B) and 169 minutes (group C), and after APSAC 188 minutes (group D). These were all in agreement with greater than 12 hour duration of changes in other markers of systemic fibrinolysis (euglobulin lysis time) and substrates depletion (fibrinogen, plasminogen, alpha 2 antiplasmin). In extended pilot clinical groups given identical thrombolytic regimens during full anticoagulation with heparin, angiographic coronary patency was found in 83% (35 of 42) after intracoronary SK (group 1), in 73 and 75%, respectively, after 500,000 IU (31 of 43) and 1.5 X 10(6) IU (30 of 40) (group 2 and 3, difference not significant) and 80% (8 of 10) after the 30-U bolus of APSAC (group 4). The overall hemorrhagic risk was 24%, equally distributed among the 4 regimens and mostly (91%) related to catheters. The incidence of bleeding unrelated to vessel puncture was 4%; no deaths occurred. It is concluded that APSAC is the most fibrinolytic regimen but its potential thrombolytic superiority over SK remains to be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
Col
J J
JJ
Department of Intensive Medicine, St. Luc Hospital, Catholic University of Louvain, Brussels, Belgium.
Col-De Beys
C M
CM
Renkin
J P
JP
Lavenne-Pardonge
E M
EM
Bachy
J L
JL
Moriau
M H
MH
D000368:Aged; D016255:Anistreplase; D001780:Blood Coagulation Tests; D001803:Blood Transfusion; D004334:Drug Administration Schedule; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010958:Plasminogen / Q000008:administration & dosage; D012008:Recurrence; D012306:Risk; D013300:Streptokinase / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014654:Vascular Patency
D016255:Anistreplase; D010958:Plasminogen; D006493:Heparin; D013300:Streptokinase