Effect of pexelizumab on mortality in patients with acute myocardial infarction or undergoing coronary artery bypass surgery: a systematic overview
Mahaffey, Kenneth W × Van de Werf, Frans Shernan, Stanton K Granger, Christopher B Verrier, Edward D Filloon, Thomas G Todaro, Thomas G Adams, Peter X Levy, Jerrold H Hasselblad, Vic Armstrong, Paul W #
American Heart Journal vol:152 issue:2 pages:291-6
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.