A double blind comparison of enoxaparin (a low molecular weight heparin) with standard heparin in the treatment of unstable coronary artery disease "The essence trial"

Background: Combination therapy with aspirin plus heparin reduces the risk of recurrent ischaemic events in patients with unstable angina (UA) and non-Q MI. Low molecular weight heparins (LMWH), with high and Xa activity, have advantages over unfractionated heparin (UH) that may result in greater efficacy and safety. Methods: In 3171 patients we compared fixed dose subcutaneous enoxaprin (LMWH) (n=1607) 1mg/kg q 12H + ASA with intravenous UH (n=1564) (adjusted by a predetermined nonogram) + ASA in the initial treatment of UA in a double blind randomised trial. Results: At 14 days, the primary end-point of the study, the composite risk of death, myocardial infarction, or recurrent angina with ECG changes or prompting intervention, was significantly lower in patients assigned to enoxaparin compared to UH (16.5% vs 19.8%: odds ratio 0.80 [95% CI O.49-0.95]; p=0.019). At 30 days, the composite outcome remained significantly lower in the enoxaparin group (19.8% vs 23.3% p=0.017). The rate of revascularisation procedures by 30 days was also significantly lower in patients in the enoxaparin group compared to the UH (27.7% vs 32.4% p=0.01). There was no difference in the incidence of major bleeding complications (6.5 vs 7.0% p=NS) but minor bleeding (largely at injection sites) was more common with enoxaparin (total: 18.4% vs 14.1%, P=0.001). Interpretation: Antithrombotic therapy with subcutaneous enoxaparin (LMWH) plus aspirin is superior to UH plus aspirin in patients with unstable angina or non-Q wave myocardial infarction at 14 days, with effects sustained at 30 days,and without an increase in clinically important bleeding. The trial has implications for the practical management of patients with Acute Coronary Syndromes.