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.

Abstract

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.

• Authors: Pierre Théroux, Paul W Armstrong, Kenneth W Mahaffey, Judith S Hochman, Kevin J Malloy, Scott Rollins, Jose C Nicolau, Joel Lavoie, The Minh Luong, Jeb Burchenal, Christopher B Granger
• Journal: European heart journal (Eur Heart J) Vol. 26 Issue 19 Pg. 1964-70 (Oct 2005) ISSN: 0195-668X [Print] England
• PMID: 15872036 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Biomarkers
• Complement C5
• Interleukin-6
• Single-Chain Antibodies
• Tumor Necrosis Factor-alpha
• C-Reactive Protein
• pexelizumab

Topics

• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Complement C5 (antagonists & inhibitors)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Interleukin-6 (blood)
• Male
• Middle Aged
• Myocardial Infarction (blood, drug therapy, mortality)
• Single-Chain Antibodies
• Treatment Outcome
• Tumor Necrosis Factor-alpha (analysis)