Effect of pexelizumab on mortality in patients with acute myocardial infarction or undergoing coronary artery bypass surgery: a systematic overview.
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.
Mahaffey
Kenneth W
KW
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. mahaf002@mc.duke.edu
Van de Werf
Frans
F
Shernan
Stanton K
SK
Granger
Christopher B
CB
Verrier
Edward D
ED
Filloon
Thomas G
TG
Todaro
Thomas G
TG
Adams
Peter X
PX
Levy
Jerrold H
JH
Hasselblad
Vic
V
Armstrong
Paul W
PW
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5 / Q000037:antagonists & inhibitors; D001026:Coronary Artery Bypass / Q000401:mortality*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D015427:Reperfusion Injury / Q000517:prevention & control; D057127:Single-Chain Antibodies
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D007155:Immunologic Factors; D057127:Single-Chain Antibodies; C402724:pexelizumab