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European Heart Journal Advance Access originally published online on January 26, 2005
European Heart Journal 2005 26(5):440-446; doi:10.1093/eurheartj/ehi104
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions{at}oupjournals.org

Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome

An ENTIRE-TIMI 23 substudy

Kausik K. Ray*, David A. Morrow, C. Michael Gibson, Sabina Murphy, Elliott M. Antman and Eugene Braunwald for the ENTIRE-TIMI 23 Study Group

The TIMI Study Group and Cardiovascular Division, Department of Medicine, Brigham & Women's Hospital/Harvard Medical School, Boston, MA, USA

Received 15 July 2004; revised 14 November 2004; accepted 25 November 2004; online publish-ahead-of-print 26 January 2005.

* Corresponding author: TIMI Study Group, 350 Longwood Avenue, First Floor, Boston, MA 02115, USA. Tel: +1 617 525 6865; fax: +1 617 734 7329. E-mail address: kkray{at}partners.org

See page 421 for the editorial comment on this article (doi:10.1093/eurheartj/ehi125)

Aims Prior studies suggest that acute coronary syndromes (ACSs) are associated with endothelial activation and that this is of prognostic significance. We hypothesized that endothelial activation, as measured by a rise in von Willebrand Factor ({Delta}vWF), was influenced by the thrombolysis in myocardial infarction flow grade (TFG), the corrected TIMI frame count (CTFC) and the choice of anticoagulant therapy after fibrinolysis in ST elevation myocardial infarction (STEMI).

Methods and results Data were drawn from the enoxaparin and tenecteplase tissue plasminogen activator (TNK-tpa) with or without GPIIb/IIIa inhibitor as the reperfusion strategy in the STEMI trial (ENTIRE-TIMI 23). Three hundred and fourteen patients had serial measurements of vWF (baseline and 48–72 h) and angiographic data available. TFG<3 (P=0.0042) or CTFC≥40 at 60 min (P=0.0035) were associated with a higher {Delta}vWF. {Delta}vWF ≥75th percentile was associated with a higher incidence of death or myocardial infarction (MI) at 30 days, compared with <75th percentile (11.2 vs. 4.1%, P=0.027). Enoxaparin independently reduced the {Delta}vWF (P=0.019) and also the composite of death or MI (OR 0.33, 95% CI 0.12–0.91, P=0.03) compared with unfractionated heparin.

Conclusion In STEMI treated by fibrinolysis, coronary flow at 60 min and choice of adjunctive anticoagulant appear to be independent determinants of {Delta}vWF. Enoxaparin is independently associated with a reduction in {Delta}vWF and a reduction in death or MI. The clinical benefits of enoxaparin as an adjunctive treatment in STEMI may be mediated in part by a reduction in vWF release.

Key Words: vWF • TIMI flow grade • Corrected TIMI frame count • ST elevation myocardial infarction • Endothelial activation


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