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.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Théroux
Pierre
P
Montreal Heart Institute, Montreal, 5000 Belanger E, Montreal, Quebec, Canada H1T 1C8. pierre.theroux@icm-mhl.org
Armstrong
Paul W
PW
Mahaffey
Kenneth W
KW
Hochman
Judith S
JS
Malloy
Kevin J
KJ
Rollins
Scott
S
Nicolau
Jose C
JC
Lavoie
Joel
J
Luong
The Minh
TM
Burchenal
Jeb
J
Granger
Christopher B
CB
D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D057127:Single-Chain Antibodies; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D003182:Complement C5; D015850:Interleukin-6; D057127:Single-Chain Antibodies; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; C402724:pexelizumab