Dose-ranging trial of enoxaparin for unstable angina: results of TIMI 11A. The Thrombolysis in Myocardial Infarction (TIMI) 11A Trial Investigators.
OBJECTIVE
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.
D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy*; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010349:Patient Compliance; D015912:Thrombolytic Therapy
D000925:Anticoagulants; D017984:Enoxaparin