Disappointing result for acadesine

Jul 12 2012

By Piriya Mahendra

The adenosine-regulating agent acadesine does not reduce the occurrence of adverse outcomes in patients undergoing on-pump coronary artery bypass graft (CABG) surgery, researchers say.

Their study showed that the primary composite outcome of all-cause mortality, nonfatal stroke, or need for mechanical support for severe left ventricular dysfunction (SLVD) during and after CABG surgery through postoperative day 28 occurred in 75 (5.0%) of 1493 participants in the placebo group and 76 (5.1%) of 1493 participants in the acadesine group.

"The incidence of the primary composite endpoint in the overall study population (including the placebo group) was substantially below that projected from the previous studies and historical data," comment Mark Newman (Duke University, Durham, North Carolina, USA) and team.

There was no statistically significant difference between the groups with regard to the secondary endpoints measured, including myocardial infarction 24 hours after surgery, hospitalization, and new atrial fibrillation.

Significantly, results of a prespecified futility analysis indicated a very low likelihood for a statistically significant efficacious outcome, which led to the termination of the trial after 3080 of the originally projected 7500 participants were randomized.

The Reduction in Cardiovascular Events by Acadesine in patients Undergoing CABG (RED-CABG) trial included participants with a median age of 66 years who were undergoing CABG surgery with cardiopulmonary bypass and were at intermediate or high risk for postoperative adverse events.

All participants were randomly allocated in a 1:1 ratio to receive treatment with acadesine (0.1 mg/kg per minute for 7 hours) or placebo just before anesthesia induction.

The authors suggest that the negative results they observed in the study may have been due to the eligibility criteria they defined. "We cannot exclude the possibility that a more favorable result might have been obtained in patients deemed to be at higher risk of intraoperative ischemic events," they explain.

"The incidence of the primary composite endpoint was 5%, indicating the need for continued investigation into therapies to reduce perioperative morbidity and mortality," they write in JAMA. "However, effective therapies remain elusive."

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