Safety and Efficacy of Unfractionated Heparin Versus Enoxaparin
Background: The advantages of enoxaparin over unfractionated heparin (UFH) for the treatment of patients with non-ST-segment elevation acute coronary syndromes are well established. However, no data are available about the safety and efficacy in patients who are obese and patients with severe renal impairment.
Methods: A retrospective analysis of treatment effects was performed on patients who were obese and patients with severe renal impairment from the Efficacy Safety Subcutaenous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials, in which patients were treated with enoxaparin or UFH. The primary composite end point was death, myocardial infarction (MI), and urgent revascularization (UR), and the secondary end points were major and any hemorrhage.
Results: When compared with UFH, enoxaparin reduced the rate of the primary end point in patients who were obese (14.3% vs 18.0%, P = .05), patients who were not obese (16.1% vs 19.2%, P <.01), and patients without severe renal impairment (15.7% vs 18.4%, P <.01). There was no significant difference in major bleeding between enoxaparin and UFH in any of the 4 subgroups. There were no differences in either the primary end point (17.6% vs 16.2%, P = .39) or major hemorrhage (1.3% vs 0.8%, P = .12) in patients who were obese receiving either UFH or enoxaparin compared with patients who were not obese. Patients with severe renal impairment tended toward a higher rate of the primary end point (25.9% vs 17%, P = .09) and experienced more major hemorrhages (6.6% vs 1.1%, P <.0001).
Conclusions: Enoxaparin reduced the rate of the combined end point of death/MI/UR in the subgroups of patients who were obese, patients who were not obese, and patients without renal insufficiency. Obesity did not impact clinical outcomes in the combined analysis of ESSENCE and TIMI 11B. Patients with severe renal impairment have a higher risk of clinical events and major and any hemorrhages than patients without severe renal impairment, whether they are treated with UFH or enoxaparin.

Patients with non-ST-segment-elevation acute coronary syndromes (NSTE ACS) are treated with antithrombotic therapy to prevent recurrent ischemic events. Current guidelines suggest initiating antiplatelet therapy with aspirin and anticoagulant therapy with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Recent studies have shown that the combination of aspirin and the LMWH, enoxaparin, is significantly more effective than the combination of aspirin and UFH in preventing ischemic complications associated with NSTE ACS. LMWH has several advantages over UFH, including a more predictable anticoagulant effect, better bioavailability, and a longer half-life. In 2 studies of patients with NSTE ACS, enoxaparin was shown to reduce the release of von Willebrand factor, an independent predictor of early adverse outcomes. UFH provided no such reduction in the release of von Willebrand factor. In addition, it is not necessary to monitor the activated partial thromboplastin time (aPTT) during treatment with LMWH, as it is during treatment with UFH. Early data suggest that patients undergoing coronary angiography or percutaneous coronary intervention (PCI) within 8 hours of a 1-mg/kg subcutaneous dose of enoxaparin have consistent therapeutic anti-factor Xa concentrations.

Despite evidence of their use in NSTE ACS, there are currently no data evaluating the safety and efficacy of LMWHs specifically in patients who are obese and patients with severe renal impairment (ie, with a creatinine clearance [CrCL] ≤30 mL/min). We have therefore performed retrospective subgroup analyses of the efficacy and safety of enoxaparin and UFH in patients who are obese and renally impaired from the combined database of the Thrombolysis in Myocardial Infarction (TIMI) 11B and Efficacy Safety Subcutaenous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) trials. The effects of enoxaparin and UFH on these outcomes were compared: the primary composite end point of death, myocardial infarction (MI), and urgent revascularization (UR) at 43 days, and secondary end points of major and any hemorrhage. The effects of obesity and renal impairment on these outcomes were also evaluated.