Superiority of enoxaparin over heparin in combination with a GPIIb/IIIa receptor antagonist during coronary thrombolysis in dogs.
It is known that a low-molecular-weight heparin (LMWH) is more effective than unfractionated heparin in unstable angina/non-Q-wave myocardial infarction (UA/NQMI) and the platelet GPIIb/IIIa receptors play an important role in acute myocardial infarction (AMI). Therefore, enoxaparin might have a similar advantage over heparin when used with a GPIIb/IIIa antagonist (RPR109891) in coronary thrombolysis. After induction of coronary thrombosis in anesthetized dogs, infusion of saline, enoxaparin, heparin, RPR109891, enoxaparin+RPR109891, or heparin+RPR109891 was initiated followed 15 min later by recombinant tissue plasminogen activator (rt-PA). The incidence of reperfusion in the enoxaparin+RPR109891- and the heparin+RPR109891-treated groups was similar, but time to reperfusion tended to be shorter for enoxaparin versus heparin. Only 43% of the vessels reoccluded in the enoxaparin+RPR109891 group, compared to 100% vessels in the heparin+RPR109891 group. Enoxaparin+RPR109891 maintained flow for a significantly longer time compared to saline, enoxaparin, heparin, and heparin+RPR109891. Enoxaparin+RPR109891 and heparin+RPR109891 increased the template bleeding time by 2- and 3-fold and activated partial thromboplastin time (APTT) by 1.3- and 3-fold, respectively. These data suggest that enoxaparin is more effective and potentially safer than heparin when combined with a GPIIb/IIIa receptor antagonist during rt-PA-induced coronary thrombolysis.
Rebello
S S
SS
Cardiovascular Biology, Aventis Pharmaceuticals, 19426, Collegeville, PA, USA. sam.rebello@aventis.com
Kasiewski
C J
CJ
Bentley
R G
RG
Morgan
S R
SR
Chu
V
V
Bostwick
J S
JS
Klein
S I
SI
Perrone
M H
MH
Leadley
R J
RJ
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D003328:Coronary Thrombosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000008:administration & dosage / Q000592:standards / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology / Q000592:standards; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013810:Therapeutic Equivalency; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology; D014654:Vascular Patency / Q000187:drug effects
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C402262:klerval; D006493:Heparin; D010959:Tissue Plasminogen Activator