Reduction of myocardial ischemic injury following coronary intervention (The MC-1 to eliminate necrosis and damage trial)

• Published in: The American journal of cardiology 2003-09, Vol.92 (6), p.660-664
• Main Authors: Kandzari, David E, Labinaz, Marino, Cantor, Warren J, Madan, Mina, Gallup, Dianne S, Hasselblad, Vic, Joseph, Diane, Allen, Andrew, Green, Cindy, Hidinger, Karl G, Krucoff, Mitchell W, Christenson, Robert H, Harrington, Robert A, Tcheng, James E
• Format: Article
• Language: English
• Subjects: Aged; Angioplasty, Balloon, Coronary - adverse effects; Cardiotonic Agents - therapeutic use; Coronary Angiography; Coronary Disease - diagnostic imaging; Coronary Disease - therapy; Double-Blind Method; Feasibility Studies; Female; Heart; Humans; Injuries; Male; Medical procedures; Middle Aged; Myocardial Ischemia - diagnostic imaging; Myocardial Ischemia - etiology; Myocardial Ischemia - prevention & control; Myocardial Reperfusion Injury - diagnostic imaging; Myocardial Reperfusion Injury - etiology; Myocardial Reperfusion Injury - prevention & control; Necrosis; Prevention; Pyridoxal Phosphate - therapeutic use
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/S0002-9149(03)00818-X

Myocardial ischemic injury complicating acute myocardial infarction (AMI) and coronary revascularization procedures remains an unresolved clinical dilemma. In preclinical studies, treatment with pyridoxal-5′-phosphate monohydrate (MC-1), a vitamin B6 metabolite, has demonstrated cardioprotective effects. Sixty patients scheduled for elective percutaneous coronary intervention (PCI) who had clinically high-risk characteristics for ischemic complications were randomized to treatment with MC-1 or placebo in a 2:1 double-blinded fashion. The primary end point was defined as infarct size as measured by area under the curve creatine kinase MB (CK-MB) enzymes. Secondary end points included periprocedural ischemia as assessed by continuous electrocardiographic monitoring, 30-day major adverse cardiac events, and net clinical safety, which included liver function testing. The primary end point, median periprocedural CK-MB area under the curve, was reduced from 32.9 ng/ml in the placebo group to 18.6 ng/ml with MC-1 treatment (p = 0.038), reflecting a shift in the distribution of CK-MB. By categorical classification, the occurrence of 30-day nonfatal AMI did not differ between groups. There were no deaths, and 30-day composite adverse event rates were similar (17.9% MC-1 vs 15.0% placebo, p = 1.0). There were no significant differences in ischemia parameters per continuous electrocardiographic monitoring, and no safety issues were identified. In this phase II pilot study, treatment of high-risk patients who underwent PCI with MC-1 was associated with a decrease in the total amount of CK-MB released after PCI. These results support the evaluation of MC-1 in pivotal trials of patients at risk for developing myocardial ischemia, infarction, or reperfusion injury.