Therapeutics and Drugs Briefs

Enoxaparin Superior to Unfractionated Heparin for Unstable Coronary Disease

Sources: Antman EM, et al. Circulation 1999;100:1593-1601; Antman EM, et al. Circulation 1999;100:1602-1608.

This pair of articles from the thrombolysis in Myocardial Infarction (TIMI) 11b investigators compares enoxaparin, a low-molecular-weight heparin (LMWH), to standard unfractionated heparin in patients hospitalized for unstable coronary artery disease. The TIMI trial enrolled patients presenting within 24 hours of chest pain onset and diagnosed with unstable angina or non-Q-wave myocardial infarction (MI). Patients undergoing urgent revascularization were excluded. Subjects were assigned in a double-blind fashion to receive either conventional therapy with unfractionated heparin (by weight-based bolus and infusion) for 3-8 days, or enoxaparin 30 mg infusion followed by a 1 mg/kg subcutaneous injection every 12 hours during hospitalization and after discharge, up to eight days. All patients received aspirin. Primary study end points were mortality, recurrent MI, and need for revascularization at eight days and 43 days.

The study enrolled 3910 patients. At eight days, 12% of the enoxaparin group had reached the end point of death or serious cardiac event, compared to 15% of patients in the unfractionated heparin group. This difference just reached statistical significance (P = 0.48, odds ratio 0.83 [95% CI, 0.69-1.00]). Enoxaparin’s advantage was essentially identical at 14 and 43 days. While there was no difference in major bleeding during the initial phase of the study, enoxaparin carried a higher rate of major bleeds during the outpatient phase of the study (2.9% vs 1.5%, P = 0.02). Antman and colleagues conclude that enoxaparin is superior to unfractionated heparin in the treatment of patients with unstable angina and non-Q-wave MI. They estimate that 21 adverse events would be avoided for every 1000 patients treated with enoxaparin therapy instead of unfractionated heparin.

The companion article is a meta-analysis including the TIMI 11b and ESSENCE 2 phase III studies,1 both comparing enoxaparin to unfractionated heparin in patients with unstable angina and non-Q-wave MI. Enoxaparin was not administered after hospital discharge in the ESSENCE trial. Pooled results showed that enoxaparin provided a consistent 20% reduction in death or nonfatal MI at all times up to 43 days from presentation. Enoxaparin carried a slightly (but significantly) higher rate of major bleeding during the acute phase (1.3% vs 1.1%, P = 0.03).

Like the glycoprotein IIb/IIIa inhibitors, enoxaparin is a drug with which emergency physicians must quickly become familiar. Both the TIMI 11b and ESSENCE 2 studies favor enoxaparin over unfractionated heparin in patients with unstable coronary syndromes. Enoxaparin appears to be far more effective in this setting than other LMWH preparations such as dalteparin and nadroparin, neither of which appears superior to unfractionated heparin in clinical studies.

Enoxaparin’s advantages extend beyond its clinical efficacy, which, while statistically better than unfractionated heparin, is not overwhelming. Unlike standard heparin, enoxaparin does not require constant infusion, and it is not necessary to monitor its anticoagulant effect with laboratory studies. The combination of these advantages makes enoxaparin a far more cost-effective drug.

Reference

1. Cohen M, et al. N Engl J Med 1997;337:447-452.