(July 26, 2012)
A drug designed to shield the heart from injury during bypass surgery failed to reduce deaths, strokes and other serious events among patients at high risk of complications, according to a large, international clinical trial involving researchers at Duke University and East Carolina University.
The study, led by Dr. Mark Newman of Duke University Medical Center and Dr. T. Bruce Ferguson, professor of cardiovascular sciences at the Brody School of Medicine at ECU, showed the drug acadesine does not reduce death, non-fatal strokes or the need for a cardiac pacemaker following coronary artery bypass graft, or CABG, surgery.
Acadesine is an agent used to regulate adenosine, a naturally occurring chemical that dilates blood vessels and can improve coronary blood flow and perfusion. The study looked at 3,080 patients at 300 sites in seven countries from May 2009 to July 2010 who had undergone non-emergency coronary artery bypass surgery. The operation works well for people with blocked arteries, but strokes, ventricular damage resulting in the need for a pacemaker and death can occur even after successful surgery.
Study participants were given either acadesine or a placebo before undergoing anesthesia before surgery. Most were white men, and the average age was 66.
One cause of complications is called ischemia reperfusion injury, which stems from changes that occur to tissue starved of oxygen during the surgery, when blood vessels are clamped to establish the grafts. This period of oxygen deprivation triggers inflammation and cell death once blood flow is restored.
Earlier evidence from smaller studies suggested acadesine, given before, during and after surgery, could offer protection by easing some of the inflammatory responses that kill cells. Most of those studies occurred before 1997, however, when the rate of serious complications was 10 percent or greater.
"What we found was that CABG outcomes have improved so much that patients considered 'high risk' based on five-to-10-year-old data are no longer high risk and have truly excellent outcomes following CABG," Ferguson said. "This probably explains in part why the drug intervention was negative."
Today, 30-day deaths following bypass surgery in the United States are less than 2 percent by national benchmarks.
The study was published July 11 in the Journal of the American Medical Association. It's available online at http://jama.jamanetwork.com/article.aspx?articleid=1216478
The study was funded by the drug company Schering-Plough. Several authors, including Newman and Ferguson, reported receiving grant support, honoraria, consulting fees and/or travel reimbursement from Schering-Plough/Merck.