Dose-Ranging Trial of Enoxaparin for Unstable Angina: Results of TIMI 11

Objectives. The Thrombolysis in Myocardial Infarction (TIMI) 11 trial compared the safety and tolerability of two weight-adjusted regimens of subcutaneous injections of enoxaparin, 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 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. fixed dose of either 60 mg (body weight ≥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 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 ischemi 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 high rate of patient compliance during the home treatment phase. Phase III trial is now underway to test the benefits of uninterrupted treatment with enoxaparin during both the in-hospital and outpatient treatment phases.