Effect of pexelizumab in coronary artery bypass graft surgery with extended aortic cross-clamp time.
BACKGROUND
Prolonged cross-clamp time during cardiac surgery increases the risk of postoperative mortality and myocardial injury. This subanalysis from the pexelizumab for reduction of infarction and mortality in coronary artery bypass grafting surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing on-pump coronary artery bypass graft surgery with or without valve surgery, assessed the impact of pexelizumab, an investigational C5 complement inhibitor, on postoperative outcomes after prolonged aortic cross-clamp time.


METHODS
The composite endpoint of death or myocardial infarction through postoperative day 30 and death alone through days 30, 90, and 180 were examined in subpopulations of patients across different cross-clamp times.


RESULTS
After prolonged cross-clamping (> or = 90 minutes), death, or myocardial infarction through day 30 and death through days 30, 90, and 180 were significantly increased in the intent-to-treat population and were even higher in patients with two or more prespecified risk factors, compared with all patients cross-clamped less than 90 minutes. Pexelizumab significantly reduced the incidence of death or myocardial infarction through day 30, and significantly reduced the incidence of mortality through day 180, in patients with two or more risk factors that required prolonged cross-clamp time. Pexelizumab also significantly reduced perioperative myocardial injury in all patients requiring prolonged cross-clamp time.


CONCLUSIONS
In this retrospective, subgroup analysis, pexelizumab reduced postoperative morbidity and myocardial injury in patients with multiple risk factors who underwent prolonged cross-clamp time during coronary artery bypass surgery. The clinical benefit of pexelizumab may be related to the effect of complement inhibition in the presence of potential ischemic-reperfusion injury associated with prolonged aortic cross-clamp time.
Smith
Peter K
PK
Duke University Medical Center, Durham, North Carolina 27710, USA. smith058@mc.duke.edu
Carrier
Michel
M
Chen
John C
JC
Haverich
Axel
A
Levy
Jerrold H
JH
Menasché
Philippe
P
Shernan
Stanton K
SK
Van de Werf
Frans
F
Adams
Peter X
PX
Todaro
Thomas G
TG
Verrier
Edward
E
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001011:Aorta; D015415:Biomarkers; D003167:Complement Activation / Q000187:drug effects; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D003250:Constriction; D001026:Coronary Artery Bypass; D052279:Creatine Kinase, MB Form / Q000097:blood; D004311:Double-Blind Method; D005500:Follow-Up Studies; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D015994:Incidence; D015993:Life Tables; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control* / Q000601:surgery; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D011292:Premedication; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D057127:Single-Chain Antibodies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D003182:Complement C5; D057127:Single-Chain Antibodies; C402724:pexelizumab; D052279:Creatine Kinase, MB Form