A study published on July 10 in The Journal of the American Medical Association (JAMA) found that "acadesine did not reduce the composite of all-cause mortality, nonfatal stroke or severe left ventricular dysfunction (SLVD) in a population of intermediate- to high-risk patients undergoing coronary artery bypass graft (CABG) surgery."
Previous smaller studies have shown the use of acadesine to be correlated with significant reductions in the occurrence of perioperative myocardial infarction (MI), cardiac death through postoperative day four, and a composite of cardiac death, stroke and MI. Based on the meta-analysis results of these studies, the authors aimed to "assess whether acadesine could reduce the composite of all-cause mortality, nonfatal stroke, or need for mechanical support for severe SLVD occurring during and after CABG surgery through postoperative day 28."
The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) Trial was a multi-center, "randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients undergoing nonemergency, on-pump CABG surgery at 300 sites in seven countries...Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for seven hours) or placebo (both also added to cardioplegic solutions)."
The trial was stopped due to the low likelihood of a statically significant efficacious outcome after 3,080 of the originally projected 7,500 subjects participated. "The primary outcome occurred in 75 of 1,493 participants (5 percent) in the placebo group and 76 of 1,493 (5.1 percent) in the acadesine group (odds ratio, 1.01 [95 percent CI, 0.73-1.41])."
Based on these results the authors concluded that in this population, "acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD." The authors note that since the incidence of the primary composite end point was 5 percent, this indicates "the need for continued investigation into therapies to reduce perioperative morbidity and mortality."
The authors add that "their findings illustrate inherent risks of using promising meta-analysis results to plan 'confirmatory' clinical trials."
However, "despite the lack of effect of acadesine in this population, the study also allowed the evaluation of quality of life after CABG surgery," add the authors. The findings "suggest that quality of life improves after cardiac surgery – results consistent with previous smaller studies."