title: Reduction of myocardial ischemic injury following coronary intervention (the MC-1 to Eliminate Necrosis and Damage trial).
abstract: 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.
authors.affiliation: Duke Clinical Research Institute, Durham, NC 27715, USA. kandz002@mc.duke.edu
authors.forename: David E
authors.initials: DE
authors.lastname: Kandzari
authors.forename: Marino
authors.initials: M
authors.lastname: Labinaz
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Cantor
authors.forename: Mina
authors.initials: M
authors.lastname: Madan
authors.forename: Dianne S
authors.initials: DS
authors.lastname: Gallup
authors.forename: Vic
authors.initials: V
authors.lastname: Hasselblad
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph
authors.forename: Andrew
authors.initials: A
authors.lastname: Allen
authors.forename: Cindy
authors.initials: C
authors.lastname: Green
authors.forename: Karl G
authors.initials: KG
authors.lastname: Hidinger
authors.forename: Mitchell W
authors.initials: MW
authors.lastname: Krucoff
authors.forename: Robert H
authors.initials: RH
authors.lastname: Christenson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: James E
authors.initials: JE
authors.lastname: Tcheng
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000628:therapy*; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000209:etiology* / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000209:etiology* / Q000517:prevention & control*; D009336:Necrosis; D011732:Pyridoxal Phosphate / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D011732:Pyridoxal Phosphate