Initial experience with the low-molecular-weight heparin, enoxaparin, in combination with the platelet glycoprotein IIb/IIIa blocker, tirofiban, in patients with non-ST segment elevation acute coronary syndromes.
Enoxaparin, a low-molecular-weight heparin, and tirofiban, an intravenous platelet glycoprotein IIb/IIIa receptor antagonist, have each been shown to be effective in reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. In a pilot study (ACUTE I), fifty-five patients with non-Q wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microg/kg/min intravenously) for 48/108 hours co-administered with either enoxaparin (1 mg/kg sc q 12 hours) (n = 26) or unfractionated heparin (intravenous, adjusted to activated partial thromboplastin time) (n = 27). Co-administration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was similar for enoxaparin and unfractionated heparin-treated patients. When combined with tirofiban, enoxaparin, relative to unfractionated heparin, resulted in less variability and a trend toward greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation (> 70%) in the tirofiban and enoxaparin group (84% versus 65%; p = 0.19). Median bleeding time was 21 minutes for tirofiban and enoxaparin versus 30 minutes for tirofiban and unfractionated heparin (p = non-significant). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 versus 24.9 minutes, respectively; p = 0.02). There were no major or minor bleeding events in either group by the TIMI criteria. The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin versus tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These observations have now been extended to more than 500 patients.
Cohen
M
M
Division of Cardiology, Department of Medicine, MCP-Hahnemann University School of Medicine, Philadelphia, PA, USA. marc.cohen@tenethealth.com
D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D017984:Enoxaparin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012449:Safety; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D017984:Enoxaparin; D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban