Randomized evaluation of the safety and efficacy of enoxaparin versus unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide.
BACKGROUND
Current pharmacotherapeutic options for high-risk non-ST-segment elevation acute coronary syndrome patients include aspirin, clopidogrel, heparin, and platelet glycoprotein IIb/IIIa inhibition. A key issue of uncertainty is the safety and efficacy of combination glycoprotein IIb/IIIa inhibitor and low-molecular-weight heparin therapy.


RESULTS
We randomized 746 patients with rest ischemic discomfort within 24 hours after the onset of symptoms and ST-segment deviation and/or elevation of serum cardiac markers to receive open-label enoxaparin (1 mg/kg subcutaneously twice daily) or unfractionated heparin (70-U/kg bolus; 15 U x kg(-1) x h(-1) infusion, titrated to an activated partial thromboplastin time of 1.5 to 2 times control) for 48 hours. All patients received aspirin and eptifibatide (180- microg/kg bolus; 2 microg x kg(-1) x min(-1) infusion). Major non-coronary artery bypass surgery-related bleeding at 96 hours (primary safety outcome) was significantly lower among enoxaparin-treated patients than among heparin-treated patients (1.8% versus 4.6%, P=0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, P=0.003). Patients in the enoxaparin group were less likely to experience ischemia as detected by continuous ECG evaluation (primary efficacy outcome) during the initial (14.3% versus 25.4%, P=0.0002) and subsequent (12.7% versus 25.9%, P<0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, P=0.031).


CONCLUSIONS
When aspirin and eptifibatide are used in high-risk non-ST-segment elevation acute coronary syndrome patients, enoxaparin improves outcomes (determined on the basis of better safety and efficacy) compared with currently recommended unfractionated heparin therapy and provides a useful novel alternative therapeutic strategy.
Goodman
Shaun G
SG
Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. goodmans@smh.toronto.on.ca
Fitchett
David
D
Armstrong
Paul W
PW
Tan
Mary
M
Langer
Anatoly
A
D000208:Acute Disease; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy*; D004562:Electrocardiography; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D000077542:Eptifibatide; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D017202:Myocardial Ischemia / Q000517:prevention & control; D010455:Peptides / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome
D017984:Enoxaparin; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006493:Heparin; D000077542:Eptifibatide; D001241:Aspirin