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European Heart Journal Advance Access originally published online on May 4, 2005
European Heart Journal 2005 26(19):1964-1970; doi:10.1093/eurheartj/ehi292
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Prognostic significance of blood markers of inflammation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty and effects of pexelizumab, a C5 inhibitor: a substudy of the COMMA trial

Pierre Théroux1,*, Paul W. Armstrong2, Kenneth W. Mahaffey3, Judith S. Hochman4, Kevin J. Malloy5, Scott Rollins6, Jose C. Nicolau7, Joel Lavoie1, The Minh Luong1, Jeb Burchenal8 and Christopher B. Granger3

1Montreal Heart Institute, Montreal, 5000 Belanger E, Montreal, Quebec, Canada H1T 1C8
2University of Alberta, Edmonton, Alberta, Canada
3Duke Clinical Research Institute, Durham, NC, USA
4New York University School of Medicine, New York, NY, USA
5Procter & Gamble Pharmaceuticals, Mason, OH, USA
6Alexion Pharmaceuticals, Inc., Cheshire, CT, USA
7Heart Institute, University of Sao Paulo Medical School, Sao Paulo, Brazil
8South Denver Cardiology Associates, Denver, CO, USA

Received 26 November 2004; revised 7 March 2005; accepted 24 March 2005; online publish-ahead-of-print 4 May 2005.

* Corresponding author: Tel: 514 376 3330 3616; fax: 514 376 1076. E-mail address: pierre.theroux{at}icm-mhi.org

Aims Pexelizumab, a monoclonal antibody inhibiting C5, reduced 90 day mortality and shock in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial without apparent reductions in infarct size. Inflammation is a critical component of ST-elevation myocardial infarction (STEMI); this substudy examines prognostic values of selected markers and treatment effects.

Methods and results C-reactive protein, interleukin-6 (IL-6), and tumour necrosis factor-{alpha} (TNF-{alpha}) serum levels were assessed in 337 patients enrolled in either the placebo or the pexelizumab 24 h infusion group. Higher C-reactive protein and IL-6 levels at baseline, 24 h, and 72 h were strongly associated with increased subsequent death (P<0.002 at baseline and 24 h, P<0.02 at 72 h); and all baseline marker levels with death or cardiogenic shock (P<0.03) within 90 days. C-reactive protein and IL-6 levels were similar at baseline, but significantly lower 24 h later with pexelizumab, when compared with placebo (17.1 vs. 25.5 mg/L, P=0.03 and 51.0 vs. 63.8 pg/mL, P=0.04, respectively). At 72 h, corresponding levels were similar, whereas TNF-{alpha} was slightly higher (P=0.04) in the treated group.

Conclusion Inflammation markers and their serial changes predict death and shock in patients with STEMI undergoing primary angioplasty. Pexelizumab reduced C-reactive protein and IL-6, suggesting treatment benefits mediated through anti-inflammatory effects.

Key Words: Myocardial infarction • Primary angioplasty • Complement inhibition • Pexelizumab • C-reactive protein • Interleukin-6 • Tumour necrosis factor


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