Efficacy and safety of pyridoxal 5'-phosphate (MC-1) in high-risk patients undergoing coronary artery bypass graft surgery: the MEND-CABG II randomized clinical trial.
BACKGROUND
Coronary artery bypass graft (CABG) surgery is frequently performed and effective; however, perioperative complications related to ischemia-reperfusion injury, including myocardial infarction (MI), remain common and result in significant morbidity and mortality. MC-1, a naturally occurring pyridoxine metabolite and purinergic receptor antagonist, prevents cellular calcium overload and may reduce ischemia-reperfusion injury. Phase 2 trial data suggest that MC-1 may reduce death or MI in high-risk patients undergoing CABG surgery.


OBJECTIVE
To assess the efficacy and safety of MC-1 administered immediately before and for 30 days after surgery in patients undergoing CABG surgery.


METHODS
The MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II Trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, with 3023 intermediate- to high-risk patients undergoing CABG surgery with cardiopulmonary bypass enrolled between October 2006 and September 2007 at 130 sites in Canada, the United States, and Germany.


METHODS
Patients received either MC-1, 250 mg/d (n = 1519), or matching placebo (n = 1504) immediately before and for 30 days after CABG surgery.


METHODS
The primary efficacy outcome was cardiovascular death or nonfatal MI, defined as a creatine kinase (CK) MB fraction of at least 100 ng/mL or new Q waves through postoperative day 30.


RESULTS
The primary efficacy outcome occurred in 140 of 1510 patients (9.3%) in the MC-1 group and 133 of 1486 patients (9.0%) in the placebo group (risk ratio, 1.04; 95% confidence interval, 0.83-1.30; P = .76). All-cause mortality was higher among patients assigned to MC-1 than placebo at 4 days (1.0% vs 0.3%; P = .03) but was similar at 30 days (1.9% vs 1.5%; P = .44). There was no difference in the 8- to 24-hour CK-MB area under the curve between the MC-1 and placebo groups (median, 270 [interquartile range, 175-492] vs 268 [interquartile range, 170-456] hours x ng/mL; P = .11).


CONCLUSIONS
In this population of intermediate- to high-risk patients undergoing CABG surgery, MC-1 did not reduce the composite of cardiovascular death or nonfatal MI.


BACKGROUND
clinicaltrials.gov Identifier: NCT00402506
Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina 27715 , USA. john.h.alexander@duke.edu
Alexander
John H
JH
Emery
Robert W
RW
Carrier
Michel
M
Ellis
Stephen J
SJ
Mehta
Rajendra H
RH
Hasselblad
Vic
V
Menasche
Philippe
P
Khalil
Ahmad
A
Cote
Robert
R
Bennett-Guerrero
Elliott
E
Mack
Michael J
MJ
Schuler
Gerhard
G
Harrington
Robert A
RA
Tardif
Jean-Claude
JC
D000368:Aged; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology* / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000517:prevention & control*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000627:therapeutic use*; D012306:Risk
D002121:Calcium Channel Blockers; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate