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Effect of Adenosine-Regulating Agent Acadesine on Morbidity and Mortality Associated With Coronary Artery Bypass Grafting. The RED-CABG Randomized Controlled Trial
Study Questions:
What is the efficacy and safety of acadesine administered in the perioperative period of coronary artery bypass grafting (CABG) in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days?
Methods:
The RED-CABG (Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG) trial was 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. Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg/min for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction. The main outcome measure was the 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 3,080 of the originally projected 7,500 study participants were randomized. The primary outcome occurred in 75 of 1,493 participants (5.0%) in the placebo group and 76 of 1,493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% confidence interval, 0.73-1.41]). There were no differences in key secondary endpoints measured.
Conclusions:
The authors concluded that acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD.
Perspective:
This study suggests that in a population of intermediate- to high-risk patients undergoing CABG surgery, acadesine had no effect on the composite endpoint of all-cause mortality, nonfatal stroke, and SLVD requiring mechanical support through postoperative day 28. These findings further highlight inherent risks of using promising meta-analysis results to plan confirmatory clinical trials. The incidence of the primary composite endpoint was quite high at 5%, indicating the need for continued research in novel therapies to reduce perioperative morbidity and mortality after CABG.
Keywords: Odds Ratio, Risk, Stroke, Morbidity, Perioperative Period, Postoperative Period, Cardioplegic Solutions, Ribonucleosides, Cardiovascular Diseases, Medical Futility, Confidence Intervals, Coronary Artery Bypass, Ventricular Dysfunction, Left
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