Abstract 1815: Protective Effect of Pyridoxal-5-phosphate on Perioperative Myocardial Infarction is not Dependent of Aortic Cross Clamp Time: Results from the MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Trial
Background: Aortic cross-clamp time remains a significant marker of mortality and morbidity after coronary artery bypass graft surgery (CABG). MC-1, a metabolite of pyridoxine blocking purinergic receptors and intracellular influx of Ca2+, was shown to decrease the incidence of myocardial infarction after CABG in the prospective, randomized, double-blind MEND-CABG clinical trial.
Methods: We studied the effects of treatment with MC-1 and ischemia associated with aortic cross-clamping on the incidence of CV death, myocardial infarction and cerebral infarction in the MEND-CABG trial that involved 902 high-risk patients who underwent CABG with cardiopulmonary bypass. Patients were randomized to receive either placebo, MC-1 250 mg/day or MC-1 750 mg/day starting 6 hours before CABG and continued for 30 days after surgery. Serial CK-MB determinations, ECGs and clinical evaluations were performed during the first 4 days after CABG and then at days 30 and 90. Clinical events were adjudicated centrally by an independent committee.
Results: 861 patients among which 113 had an event (CV death or MI or cerebral infarction at day 90 after CABG) (113/861, 13%) were available for the analysis. Cross-clamping time increased the event rate with an odds ratio of 1.7 (1.2 – 2.4, p = 0.0017). Treatment with MC-1 decreased the rate of events (p = 0.0455) with odds ratios of 0.57 (confidence interval (CI): 0.35 – 0.93, MC-1 250 mg/day vs. placebo) and 0.63 (CI: 0.39 – 1.02, MC-1 750 mg/day vs. placebo). There was no interaction between cross-clamp time and the effect of MC-1 (p = 0.35) on the occurrence of studied clinical endpoints.
Conclusion: MC-1 decreased the incidence of MI, cerebral infarction and CV death 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.