Management of acute coronary syndromes with low molecular weight heparin: TIMI 11A and 11B.
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The role of antithrombotic therapy has been studied in patients with acute coronary ischemia without ST segment elevation. Unfractionated heparin (UFH) has been found to decrease the rate of myocardial infarction (MI), and to reduce overall mortality and recurrent MI in a series of trials in patients with unstable angina and non-Q wave MI. UFH is limited due to its unpredictable antithrombotic effect, poor bioavailability when given subcutaneously, requirement for hospitalization and need for frequent laboratory monitoring. Conversely, low molecular weight heparins (LMWHS) offer a number of advantages over UFH. LMWHs have a predictable antithrombotic response, good bioavailability following subcutaneous administration and longer half-life than UFH, require less frequent monitoring than UFH and can be administered in fixed or weight-adjusted subcutaneous dosages once or twice daily. The safety and efficacy of the LMWH enoxaparin are evaluated in the Thrombolysis in Myocardial Infarction (TIMI) 11 program. TIMI 11 A was designed to compare the safety and tolerability of two dosage regimens of enoxaparin in patients with unstable angina or non-Q wave MI, whereas TIMI 11B was designed as a phase III trial, comparing the efficacy and safety of enoxaparin with those of UFH in the acute phase, and the efficacy and safety of extended administration of LMWH with those of placebo for 45 days. TIMI 11A found that the rate of major hemorrhage was significantly lower for the lower enoxaparin dose (1.0 mg/kg). The results of the published studies indicate that LMWHs are effective in reducing major ischemic outcomes in patients with unstable angina and non-Q wave MI. The results of the TIMI 11B trial will be available in late 1998.
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