Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin versus intravenous unfractionated heparin, in non-Q-wave Coronary Events.
Combination antithrombotic therapy with heparin plus aspirin decreases the risk of recurrent ischemic events in patients with acute coronary syndromes without persistent ST-segment elevation. Compared with standard unfractionated heparin, low-molecular-weight heparin (LMWH) has a more predictable antithrombotic effect, is easier to administer, and does not require coagulation monitoring. At 176 hospitals in 3 continents, 3,171 patients with rest unstable angina or non-wave myocardial infarction were randomly assigned to either enoxaparin (a LMWH), 1 mg/kg twice daily subcutaneously, or to continuous intravenous unfractionated heparin, for a minimum of 48 hours to a maximum of 8 days. Trial medication was administered in a double-blind, placebo-controlled fashion. At 14 days, the primary endpoint, the composite risk of death, myocardial infarction, or recurrent angina with electrocardiographic changes or prompting intervention, was significantly lower in patients assigned to enoxaparin compared with heparin (16.6% vs 19.8%; odds ratio [OR] 1.24; 95% confidence interval [CI] 1.04-1.49; p = 0.019). At 30 days, the composite risk of death, myocardial infarction, or recurrent angina remained significantly lower in the enoxaparin group compared with the unfractionated heparin group (19.8% vs 23.3%, OR 1.23; 95% CI 1.0-1.46, p = 0.016). The rate of revascularization procedures at 30 days was also significantly lower in patients assigned to enoxaparin (27.1% vs 32.2%, p = 0.001). The 30-day incidence of major bleeding complication was 6.5% versus 7.0% (p = not significant), but the incidence of minor bleeding was significantly higher in the enoxaparin group (13.8% vs 8.8%, p <0.001) due primarily to injection-site ecchymosis. Thus, combination antithrombotic therapy with enoxaparin plus aspirin is more effective than unfractionated heparin plus aspirin in decreasing ischemic outcomes in patients with unstable angina or non-Q-wave myocardial infarction in the early (30 days) phase. The lower recurrent ischemic event rate seen with the LMWH, enoxaparin, is achieved without an increase in major bleeding, but with an increase in minor bleeding complications due mainly to injection-site ecchymosis.
Cohen
M
M
Division of Cardiology, Allegheny University of the Health Sciences-Hahnemann Division, Philadelphia, Pennsylvania 19102-1192, USA.
Demers
C
C
Gurfinkel
E P
EP
Turpie
A G
AG
Fromell
G J
GJ
Goodman
S
S
Langer
A
A
Califf
R M
RM
Fox
K A
KA
Premmereur
J
J
Bigonzi
F
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D004311:Double-Blind Method; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D012008:Recurrence; D012449:Safety; D015996:Survival Rate; D016896:Treatment Outcome
D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D010975:Platelet Aggregation Inhibitors; D001241:Aspirin