TY - JOUR
T1 - Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting
T2 - The RED-CABG randomized controlled trial
AU - Newman, Mark F.
AU - Ferguson, T. Bruce
AU - White, Jennifer A.
AU - Ambrosio, Giuseppe
AU - Koglin, Joerg
AU - Nussmeier, Nancy A.
AU - Pearl, Ronald G.
AU - Pitt, Bertram
AU - Wechsler, Andrew S.
AU - Weisel, Richard D.
AU - Reece, Tammy L.
AU - Lira, Armando
AU - Harrington, Robert A.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/7/11
Y1 - 2012/7/11
N2 - Context: Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery by pass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine,afirst-in-class adenosine regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery. Objective: To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days. Design, Setting, and Participants: The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010. Interventions: Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction. Main Outcome Measure: Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28. Results: Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured. Conclusion: In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD. Trial Registration: clinicaltrials.gov Identifier: NCT00872001.
AB - Context: Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery by pass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine,afirst-in-class adenosine regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery. Objective: To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days. Design, Setting, and Participants: The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010. Interventions: Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction. Main Outcome Measure: Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28. Results: Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured. Conclusion: In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD. Trial Registration: clinicaltrials.gov Identifier: NCT00872001.
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U2 - 10.1001/jama.2012.7633
DO - 10.1001/jama.2012.7633
M3 - Article
C2 - 22782417
AN - SCOPUS:84863689054
SN - 0098-7484
VL - 308
SP - 157
EP - 164
JO - JAMA
JF - JAMA
IS - 2
ER -