In a randomized trial, an adenosine-regulating agent had no apparent cardioprotective effect.

Despite advances in surgical technology, ischemia/reperfusion injury associated with coronary artery bypass grafting (CABG) remains an important cause of morbidity and mortality. To evaluate the protective effect of acadesine, an adenosine-regulating agent, investigators at 300 sites in 7 countries conducted a manufacturer-sponsored, randomized, double-blind, placebo-controlled trial involving intermediate- or high-risk patients undergoing nonemergent, on-pump CABG during 2009–2010. The primary composite endpoint was all-cause mortality, nonfatal stroke, or mechanical support for severe left ventricular dysfunction during CABG or 4 weeks of follow-up.

The trial was stopped for futility after enrollment of 30% of the projected study population. The final cohort included 2986 patients (median age, 66), most of whom were white men with hyperlipidemia, diabetes, and family history of cardiovascular disease. The primary-endpoint rate was 5.0% overall and did not differ significantly between the placebo and acadesine groups (5.0% and 5.1%, respectively), as demonstrated by a Kaplan-Meier curve. No between-group difference in the rate of any secondary endpoint reached or approached statistical significance, nor was any significant difference found among groups stratified by Society of Thoracic Surgeons risk quintile.

Comment: Although previous studies yielded promising findings, this well-designed trial failed to show any benefit of acadesine on outcomes in intermediate- or high-risk patients undergoing coronary artery bypass grafting. The rate of the primary endpoint, although lower than the 10% expected with placebo in this population, underscores the need for continued efforts to prevent ischemia/reperfusion injury during and after CABG.

Source: Journal Watch Cardiology