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European Heart Journal Advance Access published online on June 28, 2007

European Heart Journal, doi:10.1093/eurheartj/ehm224
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis

Sabina A. Murphy1,*, Charles Michael Gibson1, David A. Morrow1, Frans Van de Werf2, Ian B. Menown3, Shaun G. Goodman4, Kenneth W. Mahaffey5, Marc Cohen6, Carolyn H. McCabe1, Elliott M. Antman1 and Eugene Braunwald1

1 TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, First Floor, Boston, MA 02115, USA
2 Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium
3 Craigavon Area Hospital, Northern Ireland, UK
4 Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, Toronto, Canada
5 Duke Clinical Research Institute, Durham, NC, USA
6 Newark Beth Israel Medical Center, Newark, NJ, USA

Received 18 December 2006; revised 22 March 2007; accepted 10 May 2007.

* Corresponding author. Tel: +1 617 278 0145; fax: +1 617 734 7329. E-mail address: smurphy{at}perfuse.org

Aims: To determine whether the low-molecular weight heparin enoxaparin remains favourable when compared with unfractionated heparin (UFH) among patients with acute coronary syndromes (ACS) when incorporating efficacy and safety of these adjunctive therapies using a net clinical endpoint.

Methods and results: We performed a meta-analysis of randomized trials of enoxaparin vs. UFH in ST-elevation-MI (STEMI) or non-ST-elevation-ACS (NSTEACS) (n = 49 088 patients in 12 trials). The net clinical endpoint was defined as death, MI, or major bleeding by 30 days. Death or myocardial infarction (MI) was significantly reduced with enoxaparin when compared with UFH (9.8 vs. 11.4%, OR 0.84, P < 0.001). The net clinical endpoint occurred less frequently with enoxaparin than UFH (12.5 vs. 13.5%, OR 0.90, P = 0.051). Major bleeding was higher with enoxaparin (4.3 vs. 3.4%, OR 1.25, P = 0.019). Among STEMI trials, the net clinical endpoint was significantly lower with enoxaparin (OR 0.84, P = 0.015), but there was no difference in NSTEACS trials (OR 0.97).

Conclusions: When compared with UFH, enoxaparin was associated with superior efficacy as adjunctive antithrombin therapy among >49 000 patients across the ACS spectrum. Although bleeding was increased with enoxaparin, this increase was offset by a reduction in death or MI. The net clinical benefit in favour of enoxaparin was evident among the STEMI population and was neutral among the NSTEACS population.

Key Words: Enoxaparin • Unfractionated heparin • Meta-analysis


This paper was guest edited by Prof. Freek W. A. Verheugt, University Medical Center Nijmegen, The Netherlands


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