Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: The RED-CABG randomized controlled trial

Mark F. Newman, T. Bruce Ferguson, Jennifer A. White, Giuseppe Ambrosio, Joerg Koglin, Nancy A. Nussmeier, Ronald G. Pearl, Bertram Pitt, Andrew S. Wechsler, Richard D. Weisel, Tammy L. Reece, Armando Lira, Robert A. Harrington

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume308
Issue number2
DOIs
StatePublished - Jul 11 2012

ASJC Scopus subject areas

  • Medicine (all)

Fingerprint

Dive into the research topics of 'Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: The RED-CABG randomized controlled trial'. Together they form a unique fingerprint.

Cite this