OBJECTIVES: The Thrombolysis in Myocardial Infarction (TIMI) 11A trial compared the safety and tolerability of two weight-adjusted regimens of subcutaneous injections of enoxaparin, a low molecular weight heparin, in patients with unstable angina/non-Q wave myocardial infarction (NQMI). BACKGROUND: The optimal dose of enoxaparin in patients with arterial disorders has not been established. METHODS: Patients with unstable angina/NQMI were treated over a 14-day period in an open label dose-ranging trial. During the in-hospital phase, patients received either 1.25 mg/kg body weight (dose tier 1) or 1.0 mg/kg (dose tier 2) of enoxaparin subcutaneously every 12 h. A fixed dose of either 60 mg (body weight > or = 65 kg) or 40 mg (body weight < 65 kg) was administered subcutaneously every 12 h after hospital discharge. RESULTS: In an initial cohort of 321 patients (dose tier 1), the rate of major bleeding through 14 days was 6.5% and occurred predominantly at instrumented sites. In a second cohort of 309 patients (dose tier 2), the rate of major hemorrhage was reduced to 1.9%. In both dose tiers, only 3% to 5% of patients withdrew consent for subcutaneous injections during the home treatment phase. Through 14 days, the incidence of death, recurrent myocardial infarction or recurrent ischemia requiring revascularization was 5.6% in dose tier 1 and 5.2% in dose tier 2. CONCLUSIONS: An acute phase regimen of enoxaparin (1.0 mg/kg every 12 h) is associated with an acceptable rate of major hemorrhage during the in-hospital phase. There is a high rate of patient compliance during the home treatment phase. A Phase III trial is now underway to test the benefits of uninterrupted treatment with enoxaparin during both the in-hospital and outpatient treatment phases.
OBJECTIVES: The Thrombolysis in Myocardial Infarction (TIMI) 11A trial compared the safety and tolerability of two weight-adjusted regimens of subcutaneous injections of enoxaparin, a low molecular weight heparin, in patients with unstable angina/non-Q wave myocardial infarction (NQMI). BACKGROUND: The optimal dose of enoxaparin in patients with arterial disorders has not been established. METHODS:Patients with unstable angina/NQMI were treated over a 14-day period in an open label dose-ranging trial. During the in-hospital phase, patients received either 1.25 mg/kg body weight (dose tier 1) or 1.0 mg/kg (dose tier 2) of enoxaparin subcutaneously every 12 h. A fixed dose of either 60 mg (body weight > or = 65 kg) or 40 mg (body weight < 65 kg) was administered subcutaneously every 12 h after hospital discharge. RESULTS: In an initial cohort of 321 patients (dose tier 1), the rate of major bleeding through 14 days was 6.5% and occurred predominantly at instrumented sites. In a second cohort of 309 patients (dose tier 2), the rate of major hemorrhage was reduced to 1.9%. In both dose tiers, only 3% to 5% of patients withdrew consent for subcutaneous injections during the home treatment phase. Through 14 days, the incidence of death, recurrent myocardial infarction or recurrent ischemia requiring revascularization was 5.6% in dose tier 1 and 5.2% in dose tier 2. CONCLUSIONS: An acute phase regimen of enoxaparin (1.0 mg/kg every 12 h) is associated with an acceptable rate of major hemorrhage during the in-hospital phase. There is a high rate of patient compliance during the home treatment phase. A Phase III trial is now underway to test the benefits of uninterrupted treatment with enoxaparin during both the in-hospital and outpatient treatment phases.