Abstract

CONTEXT
Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-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.

Links

Publisher Full Text

Authors

Newman MF, Ferguson TB, White JA, Ambrosio G, Koglin J, Nussmeier NA, Pearl RG, Pitt B, Wechsler AS, Weisel RD, Reece TL, Lira A, Harrington RA, RED-CABG Steering Committee and Investigators

Institution

Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. newma005@mc.duke.edu

Source

JAMA : the journal of the American Medical Association 308:2 2012 Jul 11 pg 157-64

MeSH

Adenosine
Aged
Aminoimidazole Carboxamide
Coronary Artery Bypass
Coronary Artery Disease
Double-Blind Method
Female
Humans
Male
Middle Aged
Perioperative Period
Reperfusion Injury
Ribonucleosides
Stroke
Ventricular Dysfunction, Left

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22782417