DOSE-RANGING TRIAL OF ENOXAPARIN FOR UNSTABLE ANGINA - RESULTS OF TIMI 11A

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 hepar in, in patients with unstable anginal non-Q wave myocardial infarction (NQMI). Background. The optimal dose of enoxaparin in patients with a rterial disorders has not been established. Methods. Patients with uns table angina/NQMI were treated over a 14-day period in an open label d ose ranging trial, During the in-hospital phase, patients received eit her 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 (b ody weight greater than or equal to 65 kg) or 40 mg (body weight <65 k g) was administered subcutaneously every 12 h after hospital discharge . Results. In an initial cohort of 321 patients (dose tier 1), the rat e of major bleeding through 14 days was 6.5% and occurred predominantl y 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 ti ers, only 3% to 5% of patients withdrew consent for subcutaneous injec tions during the home treatment phase, Through 14 days, the incidence of death, recurrent myocardial infarction or recurrent ischemia requir ing 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 t he in-hospital phase, There is a high rate of patient compliance durin g the home treatment phase, A Phase III trial is now underway to test the benefits of uninterrupted treatment with enoxaparin during both th e in-hospital and outpatient treatment phases. (C) 1997 by the America n College of Cardiology.