Effect of pexelizumab on mortality in patients with acute myocardial infarction or undergoing coronary artery bypass surgery: a systematic overview.

Abstract

BACKGROUND:

Recent trials evaluating the C5 complement inhibitor, pexelizumab, have shown that modulation of inflammation during ischemia/reperfusion in patients with acute myocardial infarction (MI) or undergoing coronary artery bypass graft (CABG) surgery may improve clinical outcomes.

METHODS:

We performed a systematic overview of individual patient data from all completed randomized controlled trials of pexelizumab to evaluate the effect on all-cause mortality at 30 and 180 days after treatment. We used a random effects model and included all 5916 patients randomized in 4 clinical trials. Patients received placebo, pexelizumab bolus only or pexelizumab bolus followed by a 24-hour infusion.

RESULTS:

A significant reduction in mortality at 30 days was observed in patients treated with bolus plus infusion (n = 2476) compared with placebo (n = 2492) (2.9% vs 4.2%; relative risk [RR], 0.70; 95% confidence interval [CI], 0.52-0.95; P = .02), with no interaction according to disease state of CABG or acute MI (P for interaction .33). A trend toward a reduction in mortality was observed in patients who received bolus plus infusion or bolus only (n = 3429) compared with placebo (n = 2476) (3.5% vs 4.2%; RR, 0.85; 95% CI, 0.66-1.0975; P = .215), but not in patients who received bolus only (n = 937) compared with placebo (n = 937) (5.2% vs 5.4%; RR, 0.96; 95% CI, 0.66-1.41; P = .918). The mortality benefit with bolus plus infusion compared with placebo persisted through 180 days (P = .05).

CONCLUSIONS:

Pexelizumab reduced 30-day mortality in this systematic evaluation. Bolus plus infusion dose is being studied in ongoing trials in acute MI and CABG populations.

• Authors: Kenneth W Mahaffey, Frans Van de Werf, Stanton K Shernan, Christopher B Granger, Edward D Verrier, Thomas G Filloon, Thomas G Todaro, Peter X Adams, Jerrold H Levy, Vic Hasselblad, Paul W Armstrong
• Journal: American heart journal (Am Heart J) Vol. 152 Issue 2 Pg. 291-6 (Aug 2006) ISSN: 1097-6744 [Electronic] United States
• PMID: 16875911 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Complement C5
• Immunologic Factors
• Single-Chain Antibodies
• pexelizumab

Topics

• Adult
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Complement C5 (antagonists & inhibitors)
• Coronary Artery Bypass (mortality)
• Female
• Humans
• Immunologic Factors (pharmacology, therapeutic use)
• Male
• Middle Aged
• Myocardial Infarction (drug therapy, mortality)
• Randomized Controlled Trials as Topic
• Reperfusion Injury (prevention & control)
• Single-Chain Antibodies