Post-reperfusion myocardial infarction: long-term survival improvement using adenosine regulation with acadesine.

Abstract

OBJECTIVES:

The 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).

BACKGROUND:

No 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.

METHODS:

At 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.

RESULTS:

Perioperative 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.

CONCLUSIONS:

Acadesine 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.

• Authors: Dennis T Mangano, Yinghui Miao, Iulia C Tudor, Cynthia Dietzel, Investigators of the Multicenter Study of Perioperative Ischemia (McSPI) Research Group, Ischemia Research and Education Foundation (IREF)
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 48 Issue 1 Pg. 206-14 (Jul 04 2006) ISSN: 1558-3597 [Electronic] United States
• PMID: 16814669 (Publication Type: Comment, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Ribonucleosides
• Aminoimidazole Carboxamide
• acadesine
• Adenosine

Topics

• Adenosine (metabolism)
• Aged
• Aminoimidazole Carboxamide (adverse effects, analogs & derivatives, therapeutic use)
• Coronary Artery Bypass
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Myocardial Infarction (etiology, mortality, prevention & control)
• Myocardial Reperfusion Injury (complications, metabolism)
• Preoperative Care
• Ribonucleosides (adverse effects, therapeutic use)
• Risk Factors
• Survival Rate