Background: Two large-scale phase III clinical trials, the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) trial and the Thrombolysis in Myocardial Infarction (TIMI) 11B study, have shown the low-molecular-weight heparin, enoxaparin, to be more effective than unfractionated heparin (UFH) in reducing the risk of death and severe cardiac events in patients with rest unstable angina and/or non-ST-segment elevation myocardial infarction (NSTEMI). However, patients with NSTEMI acute coronary syndromes are a heterogeneous group.
Methods: A meta-analysis using pooled data from ESSENCE and TIMI 11B was performed to examine the efficacy of enoxaparin in different patient subgroups. In addition, a statistical model was developed to test which factors best predicted an enhanced treatment effect.
Results: Enoxaparin was more effective than intravenous dose-adjusted UFH in reducing the incidence of the composite endpoint (including death, myocardial infarction or recurrent angina prompting urgent revascularization) in the majority of subgroups at 43 days after randomization. Univariate analyses revealed that there was a greater benefit with enoxaparin in patients with ST-segment deviation or elevated cardiac enzyme markers on admission, women, nonsmokers and patients with characteristics indicative of higher cardiac risk, including prior percutaneous coronary interventions, being at least 65 years old, prior angina and prior aspirin use. Multivariate statistical modelling of treatment effect revealed that ST-segment depression and electrocardiographic changes were the best predictors of an enhanced treatment effect.
Conclusions: These data reinforce previous evidence suggesting that enoxaparin administered subcutaneously twice daily may be considered as an alternative to intravenous UFH in the acute treatment of a broad range of patients with unstable coronary artery disease.