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Pexelizumab for the Reduction of Infarction and Mortality in Coronary Artery Bypass Graft II - PRIMO-CABG II
Description:
The goal of the trial was to evaluate if treatment with pexelizumab will be associated with a reduction in death or myocardial infarction (MI) at 30 days compared with placebo among patients undergoing coronary artery bypass graft (CABG) surgery.
Study Design
Patients Enrolled: 4254
Mean Follow Up: 90 days
Mean Patient Age: Mean age 66 years
Female: 40
Patient Populations:
Patients undergoing CABG with or without valve surgery, with at least two of the following risk factors: diabetes mellitus, prior coronary artery bypass graft, urgent intervention, female gender, history of neurological event, history of congestive heart failure, and 2 or more previous MIs or a recent MI.
Exclusions:
Current cardiogenic shock, acute left ventricular rupture, acute septal rupture or acute papillary muscle rupture; any active bacterial or other infection which is clinically significant; known or suspected hereditary complement deficiency.
Primary Endpoints:
Death or myocardial infarction (MI) through 30 days postoperative
Secondary Endpoints:
All-cause mortality through 90 days post-operative
New or worsening congestive heart failure (CHF) occurring during the index hospitalization or re-hospitalization for CHF through 30 days post-operative
Drug/Procedures Used:
Patients undergoing CABG with or without concomitant valve surgery were randomized in a double-blind manner to pexelizumab (2.0 mg/kg bolus + 24 hour infusion) or matching placebo immediately prior to surgery.
Principal Findings:
Urgent CABG was performed in 72% of patients. Diabetes was present in 60% of patients, and a history of congestive heart failure in 40% of patients.
The primary endpoint of death or MI at 30 days occurred in 15.2% of the pexelizumab group and 16.3% of the placebo group (relative risk reduction [RRR] 6.7%, p=0.201). Among the components of the composite, MI occurred in 12.6% of the pexelizumab group and 13.3% of the placebo group, (p=0.311) and death in 3.8% and 4.6%, respectively (RRR 17%, p=0.177). Results of the primary endpoint were similar in the different risk factor subgroups. Serious adverse events did not differ by treatment group (31.2% for pexelizumab and 32.5% for placebo). Sepsis occurred less often in the pexelizumab group (2.1% for 3.1%).
Interpretation:
Among patients undergoing coronary artery bypass graft surgery, treatment with pexelizumab was not associated with a difference in the primary endpoint of death or MI at 30 days compared with placebo.
In the PRIMO-CABG 1 trial, pexelizumab was not associated with a reduction in death or MI in the overall trial population, but was associated with improvements in several key subgroups, including those with multiple risk factors which prompted the design of the present trial. In a meta-analysis of all CABG patients in the 3 randomized trials with pexelizumab, a significant 21% risk reduction in mortality was demonstrated (p=0.043). It is unclear what the mechanism of action is for the mortality reduction given the mixed results in reduction of myocardial infarction.
References:
Smith PK, Carrier M, Chen JC, et al. Effect of pexelizumab in coronary artery bypass graft surgery with extended aortic cross-clamp time. Ann Thorac Surg. 2006 Sep;82(3):781-8.
Presented by Dr. Peter K. Smith at the March 2006 ACC Annual Scientific Session, Atlanta, GA.
Keywords: Antibodies, Monoclonal, Humanized, Myocardial Infarction, Sepsis, Risk Reduction Behavior, Saphenous Vein, Heart Failure, Risk Factors, Coronary Artery Bypass, Diabetes Mellitus, Single-Chain Antibodies
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