Protective effect of pyridoxal-5-phosphate (MC-1) on perioperative myocardial infarction is independent of aortic cross clamp time: results from the MEND-CABG trial.
OBJECTIVE
Aortic cross-clamp time remains a significant marker of mortality and morbidity after coronary artery bypass graft (CABG) surgery. Pyridoxal-5-phosphate (MC-1), blocking purinergic receptors and intracellular influx of calcium, was shown to decrease the incidence of perioperative myocardial infarction in the prospective, randomized, double-blinded MC-1 to Eliminate Necrosis and Damage in CABG (MEND-CABG) clinical trial.


METHODS
We studied the relationship between treatment with MC-1 and aortic cross-clamping relative to the incidence of cardiovascular (CV) death and myocardial infarction (MI) in the trial that enrolled 901 high-risk patients undergoing CABG with cardiopulmonary bypass. Patients were randomized to receive either placebo, MC-1 250 mg/day or MC-1 750 mg/day starting 3-10 h before CABG and continued for 30 days after surgery. Serial creatine kinase-myocardial band (CK-MB) determinations, ECGs and clinical evaluations were performed.


RESULTS
Cross-clamping time increased the event rate of death and MI with an odds ratio (95% confidence interval) of 1.67 (1.17-2.37, P=0.0044). Treatment with MC-1 decreased the rate of events (P=0.0073) with odds ratios of 0.52 (0.31-0.88 for MC-1 250 mg/day versus placebo) and 0.48 (0.29-0.82 for MC-1 750 mg/day versus placebo). There was no interaction between cross-clamp time and treatment (P=0.61) on the occurrence of the combined endpoint.


CONCLUSIONS
MC-1 decreased the incidence of CV death and MI (CK-MB >or=100 ng/mL) during the first 90 days after CABG in the MEND-CABG trial. Although longer aortic clamping time increased the risk of cardiovascular events, the protective effect of MC-1 was independent of ischemic time during CABG.
Carrier
M
M
Department of Surgery, Montreal Heart Institute and Université de Montréal, Montreal, QC, Canada. michel.carrier@icm-mhi.org
Emery
R
R
Kandzari
D E
DE
Harrington
R
R
Guertin
M C
MC
Tardif
J C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000401:mortality; D003250:Constriction; D001026:Coronary Artery Bypass; D052279:Creatine Kinase, MB Form / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000209:etiology / Q000517:prevention & control; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors
D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate; D052279:Creatine Kinase, MB Form