Effect of pexelizumab in coronary artery bypass graft surgery with extended aortic cross-clamp time.

Abstract

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.

• Authors: Peter K Smith, Michel Carrier, John C Chen, Axel Haverich, Jerrold H Levy, Philippe Menasché, Stanton K Shernan, Frans Van de Werf, Peter X Adams, Thomas G Todaro, Edward Verrier
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 82 Issue 3 Pg. 781-8; discussion 788-9 (Sep 2006) ISSN: 1552-6259 [Electronic] Netherlands
• PMID: 16928483 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Biomarkers
• Complement C5
• Single-Chain Antibodies
• pexelizumab
• Creatine Kinase, MB Form

Topics

• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Aorta
• Biomarkers
• Complement Activation (drug effects)
• Complement C5 (antagonists & inhibitors)
• Constriction
• Coronary Artery Bypass
• Creatine Kinase, MB Form (blood)
• Double-Blind Method
• Follow-Up Studies
• Heart Valve Prosthesis Implantation
• Humans
• Incidence
• Life Tables
• Myocardial Infarction (blood, etiology, prevention & control, surgery)
• Myocardial Reperfusion Injury (blood, etiology, prevention & control)
• Postoperative Complications (etiology, mortality, prevention & control)
• Premedication
• Recurrence
• Retrospective Studies
• Risk Factors
• Single-Chain Antibodies
• Survival Analysis
• Time Factors
• Treatment Outcome