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Low-Molecular-Weight Heparin for Unstable Angina
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Am Fam Physician. 1998 Jan 1;57(1):150.
The current standard of care for patients admitted to the hospital because of a non–Q-wave myocardial infarction or unstable angina consists of oral aspirin and intravenous administration of unfractionated heparin. However, this regimen is not consistently effective, since the anticoagulant response to heparin is unpredictable, and heparin may be neutralized by protein binding and platelets. Low-molecular-weight heparin has the advantage of being more predictable than unfractionated heparin in its therapeutic effect. Laboratory monitoring of anticoagulation is not required with low-molecular-weight heparin, and it is less commonly associated with thrombocytopenia. Cohen and colleagues compared the efficacy and safety of subcutaneous enoxaparin (a low-molecular-weight heparin) and intravenous heparin in patients with non–Q-wave coronary events.
The randomized multicenter trial, known as the Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events (ESSENCE) study, included 3,171 patients from Canada, Europe, South America and the United States. All of the patients had recent onset of angina, occurring within 24 hours of entry into the study and lasting at least 10 minutes. In addition, all of the patients had underlying ischemic heart disease manifested by one of the following: a previous history of myocardial infarction or bypass surgery, positive findings on an invasive or noninvasive diagnostic study, or definite electrocardiographic criteria, including ST-segment depression of at least 1 mm, new ST-segment elevation or T-wave changes in at least two leads.
Patients were randomized to receive either 1 mg per kg of enoxaparin subcutaneously every 12 hours plus intravenous placebo or intravenous heparin (usually a bolus infusion of 5,000 units) plus subcutaneous placebo injections. Treatment was continued for at least 48 hours, up to a maximum of eight days. In addition, aspirin was given in a daily dosage of 100 to 325 mg, depending on physician preference. The median duration of anticoagulant therapy was 2.6 days for both groups.
After 14 days of therapy, the risk of death, myocardial infarction and unstable angina was significantly lower among the patients who had received enoxaparin. This same pattern was seen at 30 days after treatment. The risk of the composite end point (death, myocardial infarction or recurrent angina) was 6 percent in the enoxaparin-treated patients, compared with 7.3 percent in the intravenous heparin group. Thirty days after randomization, the need for coronary revas-cularization was 27 percent in the enoxaparin group and 32 percent in the heparin group. No significant difference was apparent between the two groups in major hemorrhagic complications, but minor bleeding, most commonly ecchymosis at the injection site, occurred more frequently in the enoxaparin group.
The authors conclude that antithrombotic therapy with enoxaparin plus aspirin is more effective than intravenous heparin plus aspirin in reducing the incidence of ischemic events in patients with non–Q-wave myocardial infarction or unstable angina. A decrease in morbidity and mortality is seen for at least 30 days after initiation of therapy.
Cohen M, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997;337:447–52.
Copyright © 1998 by the American Academy of Family Physicians.
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