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Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,632
Online ISSN 1827-191X
Carrier M. 1, Emery R. 2, Kandzari D. E. 3, Harrington R. 3, Guertin M.-C. 4, Tardif J.-C. 5
1 Department of Surgery Montreal Heart Institute and Université de Montréal Montreal, QC, Canada
2 Department of Cardiovascular Surgery St. Joseph's Hospital HealthEast Care System St. Paul, MN, USA
3 Department of Interventional Cardiology Research Duke Clinical Research Institute Durham, NC, USA
4 Montreal Heart Institute Coordinating Center Montreal, QC, Canada
5 Department of Medicine Montreal Heart Institute and Université de Montréal Montreal, QC, Canada
0Aim. 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.
Conclusion. MC-1 decreased the incidence of CV death and MI (CK-MB ≥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.