Acadesine: a new drug that may improve myocardial protection in coronary artery bypass grafting. Results of the first international multicenter study. Multinational Acadesine Study Group.
The effect of acadesine, an adenosine-regulating agent, on the incidence of myocardial infarction, all adverse cardiovascular outcomes (myocardial infarction, cardiac death, left ventricular dysfunction, life-threatening arrhythmia, or cerebrovascular accident) and mortality was assessed in 821 patients undergoing coronary artery bypass grafting. Patients were prospectively stratified to a high-risk group (age > 70 years, unstable angina, previous coronary bypass, unsuccessful angioplasty, or ejection fraction < 30%) or a non-high-risk group. They were randomized in a double-blind manner to placebo (n = 418) or acadesine (n = 403) by intravenous infusion over 7 hours (0.1 mg/kg per minute) and in the cardioplegic solution (placebo or acadesine; 5 micrograms/ml). Acadesine did not significantly affect the incidence of myocardial infarction in the overall study population, but it significantly reduced the incidence of Q-wave myocardial infarction in high-risk patients (placebo, 19.7%; acadesine, 10.0%; p = 0.032). The incidences of all adverse cardiovascular outcomes (placebo, 19.4%; acadesine, 18.4%) and overall mortality (placebo, 3.4%; acadesine, 2.7%) were similar between the two treatment groups. However, acadesine reduced the incidence of cardiac related events that contributed to deaths occurring during the first 3 postoperative days so that the incidence of death in this period was lower (placebo, 1.9%; acadesine, 0.2%; p = 0.038). No adverse events were related to acadesine treatment. Although overall there were no statistically significant between-group differences for the primary study end points, a secondary analysis in a prospectively defined high-risk subgroup suggests that acadesine may be beneficial in some patients.
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002423:Cause of Death; D001026:Coronary Artery Bypass / Q000009:adverse effects* / Q000401:mortality; D003327:Coronary Disease / Q000209:etiology* / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D011446:Prospective Studies; D012044:Regression Analysis; D012263:Ribonucleosides / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome
D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine