• Jean-Claude Tardif, Michel Carrier, David E Kandzari, Robert Emery, Robert Cote, Therese Heinonen, Marjorie Zettler, Vic Hasselblad, Marie-Claude Guertin, Robert A Harrington, and MEND-CABG Investigators.
• Montreal Heart Institute, Montreal, Canada. jean-claude.tardif@icm-mhi.org
• J. Thorac. Cardiovasc. Surg. 2007 Jun 1;133(6):1604-11.

ObjectiveCoronary artery bypass graft surgery remains associated with significant postoperative cardiovascular morbidity and mortality in high-risk patients. MC-1 (pyridoxal-5'-phosphate monohydrate) inhibits purinergic receptors and intracellular influx of Ca2+, thereby reducing cellular injury during experimental ischemia and reperfusion. The MEND-CABG trial tested the hypothesis that MC-1 reduces cardiovascular morbidity and mortality after coronary artery bypass graft.MethodsIn a phase 2, double-blinded, placebo-controlled study, 901 patients scheduled for coronary artery bypass graft surgery with cardiopulmonary bypass and at high risk for subsequent cardiac or neurologic complications were randomly assigned to receive oral MC-1 (250 mg or 750 mg/d once daily) or placebo beginning 3 to 10 hours prior to surgery and continued to postoperative day 30.ResultsAt 30 days, MC-1 250 mg (compared with placebo) reduced the composite of death, nonfatal cerebral infarction, and nonfatal myocardial infarction by 14.0% (P = .3124) with peak creatinine kinase-myocardial band > or =50 ng/mL (prespecified primary end point); 32.3% (P = .0349) with peak creatinine kinase-myocardial band > or =70 ng/mL; and 37.2% (P = .0283) with peak creatinine kinase-myocardial band > or =100 ng/mL. Myocardial infarctions with peak creatinine kinase-myocardial band> or =100 ng/mL were reduced by 47.2% in the MC-1 250-mg group versus placebo (P = .0083). Greater efficacy was demonstrated with 250 mg than with the 750-mg dose of MC-1.ConclusionsIn high-risk patients undergoing coronary artery bypass graft, treatment with MC-1 did not significantly affect the prespecified primary end point but was associated with a significant reduction in perioperative myocardial infarction with creatinine kinase-myocardial band > or =100 ng/mL. A larger, well-powered trial is needed to evaluate the cardioprotective effects of MC-1.

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