1. Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial
- Author
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Newman, Mf, Ferguson, Tb, White, Ja, Ambrosio, Giuseppe, Koglin, J, Nussmeier, Na, Pearl, Rg, Pitt, B, Wechsler, As, Weisel, Rd, Reece, Tl, Lira, A, Harrington, Ra, RED CABG Steering Committee, Investigators, and Diener, Hans Christoph (Beitragende*r)
- Subjects
Male ,medicine.medical_specialty ,Adenosine ,Population ,Medizin ,Context (language use) ,Coronary Artery Disease ,Placebo ,law.invention ,Ventricular Dysfunction, Left ,Coronary artery bypass surgery ,chemistry.chemical_compound ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Coronary Artery Bypass ,Perioperative Period ,education ,Aged ,education.field_of_study ,Acadesine ,business.industry ,General Medicine ,Perioperative ,Middle Aged ,Aminoimidazole Carboxamide ,medicine.disease ,Stroke ,chemistry ,Reperfusion Injury ,Cardiology ,Female ,Ribonucleosides ,business - 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
- Published
- 2012