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Efficacy and Safety of Pyridoxal 5′-Phosphate (MC-1) in High-Risk Patients Undergoing Coronary Artery Bypass Graft Surgery: The MEND-CABG II Randomized Clinical Trial. JAMA. 2008;299(15):1777–1787. doi:10.1001/jama.299.15.joc80027
Authors/MEND-CABG II Writing Group:John H. Alexander, MD, MHS, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina; Robert W. Emery Jr, MD,
Cardiovascular Surgery, St Joseph's Hospital, St Paul, Minnesota;
Michel Carrier, MD, Montreal Heart Institute, Montreal, Quebec, Canada; Stephen J. Ellis, PhD, Duke Clinical Research Institute, Durham, North Carolina; Rajendra H. Mehta, MD, MHS, Duke Clinical Research Institute, Durham, North Carolina; Vic Hasselblad, PhD, Duke Clinical Research Institute, Durham, North Carolina; Philippe Menasche, MD, Hospital European George Pompidou, Paris, France; Ahmad Khalil, MD, PhD, Medicure International Inc, Winnipeg, Manitoba, Canada; Robert Cote, MD, Montreal Heart Institute, Montreal, Quebec, Canada; Elliott Bennett-Guerrero, MD, Duke University Medical Center, Durham, North Carolina; Michael J. Mack, MD, Cardiothoracic Surgery Associates of North Texas, Dallas; Gerhard Schuler, MD, University of Leipzig, Leipzig, Germany; Robert A. Harrington, MD, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina; Jean-Claude Tardif, MD, Montreal Heart Institute, Montreal, Quebec, Canada.
Context Coronary artery bypass graft (CABG) surgery is frequently performed and effective; however, perioperative complications related to ischemia-reperfusion injury, including myocardial infarction (MI), remain common and result in significant morbidity and mortality. MC-1, a naturally occurring pyridoxine metabolite and purinergic receptor antagonist, prevents cellular calcium overload and may reduce ischemia-reperfusion injury. Phase 2 trial data suggest that MC-1 may reduce death or MI in high-risk patients undergoing CABG surgery.
Objective To assess the efficacy and safety of MC-1 administered immediately before and for 30 days after surgery in patients undergoing CABG surgery.
Design, Setting, and Participants The MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II Trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, with 3023 intermediate- to high-risk patients undergoing CABG surgery with cardiopulmonary bypass enrolled between October 2006 and September 2007 at 130 sites in Canada, the United States, and Germany.
Interventions Patients received either MC-1, 250 mg/d (n = 1519), or matching placebo (n = 1504) immediately before and for 30 days after CABG surgery.
Main Outcome Measures The primary efficacy outcome was cardiovascular death or nonfatal MI, defined as a creatine kinase (CK) MB fraction of at least 100 ng/mL or new Q waves through postoperative day 30.
Results The primary efficacy outcome occurred in 140 of 1510 patients (9.3%) in the MC-1 group and 133 of 1486 patients (9.0%) in the placebo group (risk ratio, 1.04; 95% confidence interval, 0.83-1.30; P = .76). All-cause mortality was higher among patients assigned to MC-1 than placebo at 4 days (1.0% vs 0.3%; P = .03) but was similar at 30 days (1.9% vs 1.5%; P = .44). There was no difference in the 8- to 24-hour CK-MB area under the curve between the MC-1 and placebo groups (median, 270 [interquartile range, 175-492] vs 268 [interquartile range, 170-456] hours × ng/mL; P = .11).
Conclusion In this population of intermediate- to high-risk patients undergoing CABG surgery, MC-1 did not reduce the composite of cardiovascular death or nonfatal MI.
Trial Registration clinicaltrials.gov Identifier: NCT00402506
Trial Registration Published online April 1, 2008 (doi:10.1001/jama.299.15.joc80027).
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