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
; 299(15): 1777-87, 2008 Apr 16.
Article
em En
| MEDLINE
| ID: mdl-18381567
ABSTRACT
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, ANDPARTICIPANTS:
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 OUTCOMEMEASURES:
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 x 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
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfato de Piridoxal
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Bloqueadores dos Canais de Cálcio
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Traumatismo por Reperfusão Miocárdica
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Ponte de Artéria Coronária
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Antagonistas do Receptor Purinérgico P2
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Infarto do Miocárdio
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article