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.

Abstract

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.

• Authors: P Menasché, W R Jamieson, W Flameng, M K Davies
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 110 Issue 4 Pt 1 Pg. 1096-106 (Oct 1995) ISSN: 0022-5223 [Print] United States
• PMID: 7475138 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Ribonucleosides
• Aminoimidazole Carboxamide
• acadesine

Topics

• Aminoimidazole Carboxamide (analogs & derivatives, therapeutic use)
• Cause of Death
• Coronary Artery Bypass (adverse effects, mortality)
• Coronary Disease (etiology, prevention & control)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Myocardial Infarction (etiology, prevention & control)
• Prospective Studies
• Regression Analysis
• Ribonucleosides (therapeutic use)
• Risk Factors
• Treatment Outcome