• Dennis T Mangano, Yinghui Miao, Iulia C Tudor, Cynthia Dietzel, Investigators of the Multicenter Study of Perioperative Ischemia (McSPI) Research Group, and Ischemia Research and Education Foundation (IREF).
• Ischemia Research and Education Foundation (IREF), San Bruno, California 94066, USA. dtb@iref.org
• J. Am. Coll. Cardiol. 2006 Jul 4;48(1):206-14.

ObjectivesThe purpose of this study was to assess the safety and efficacy of the adenosine regulating agent (ARA) acadesine for reducing long-term mortality among patients with post-reperfusion myocardial infarction (MI).BackgroundNo prospectively applied therapy exists that improves long-term survival after MI associated with coronary artery bypass graft (CABG) surgery-a robust model of ischemia/reperfusion injury. Pretreatment with the purine nucleoside autocoid adenosine mitigates the extent of post-ischemic reperfusion injury in animal models. Therefore, we questioned whether use of the ARA acadesine-by increasing interstitial adenosine concentrations in ischemic tissue-would improve long-term survival after post-reperfusion MI.MethodsAt 54 institutions, 2,698 patients undergoing CABG surgery were randomized to receive placebo (n = 1,346) or acadesine (n = 1,352) by intravenous infusion (0.1 mg/kg/min; 7 h) and in cardioplegia solution (placebo or acadesine; 5 microg/ml). Myocardial infarction was prospectively defined as: 1) new Q-wave and MB isoform of creatine kinase (CK-MB) elevation (daily electrocardiography; 16 serial CK-MB measurements); or 2) autopsy evidence. Vital status was assessed over 2 years, and outcomes were adjudicated centrally.ResultsPerioperative MI occurred in 100 patients (3.7%), conferring a 4.2-fold increase in 2-year mortality (p < 0.001) compared with those not suffering MI. Acadesine treatment, however, reduced that mortality by 4.3-fold, from 27.8% (15 of 54; placebo) to 6.5% (3 of 46; acadesine) (p = 0.006), with the principal benefit occurring over the first 30 days after MI. The acadesine benefit was similar among diverse subsets, and multivariable analysis confirmed these findings.ConclusionsAcadesine is the first therapy proven to be effective for reducing the severity of acute post-reperfusion MI, substantially reducing the risk of dying over the 2 years after infarction.

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