Administration of regulating agent prior to CABG surgery does not appear to improve outcomes

July 10, 2012

Among intermediate- to high-risk patients undergoing coronary artery bypass graft surgery, administration of the agent acadesine to regulate adenosine (a naturally occurring chemical that dilates blood flow and can improve coronary blood flow and perfusion) did not reduce all-cause death, nonfatal stroke, or need for mechanical support for ventricular dysfunction, for approximately a month after surgery, according to a study in the July 11 issue of JAMA.

"Despite improvements in myocardial protection and perioperative care, the risk of death is still substantial in the first month after (CABG) surgery, averaging 3 percent to 6 percent, and can be even higher in patients with poor left ventricular function. Up to 50 percent of these deaths have been attributed to a cardiac cause, and this percentage has remained fairly constant over time," according to background information in the article. "In a meta-analysis of , perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, , and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery." The authors add that the administration of adenosine during CABG surgery is difficult to regulate and led to the development of adenosine-regulating agents, of which acadesine is the first to be tested in large-scale clinical trials.

Mark F. Newman, M.D., of Duke University Medical Center, Durham, N.C., and colleagues conducted a study designed to more definitely test whether acadesine could reduce the composite of all-cause mortality, nonfatal stroke, or need for mechanical support for severe (SLVD) occurring during and after CABG surgery through postoperative day 28. The Reduction in by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, placebo-controlled study included intermediate- to high- (median [midpoint] age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. The majority of participants were white men with a history of hyperlipidemia, diabetes, family history of cardiovascular disease, and previous percutaneous coronary intervention (procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries). Enrollment occurred from May 2009 to July 2010. Eligible participants were randomized to receive acadesine or placebo beginning just before anesthesia induction.

The trial was stopped after 3,080 of the originally projected 7,500 study participants were randomized because early analysis indicated a very low likelihood of a statistically significant efficacious outcome. The final sample size consisted of 2,986 patients in the intention to treat analysis. The researchers found that the primary efficacy outcome (composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD) was observed in 5 percent of participants overall. There was no significant difference between the placebo and acadesine groups, with incidence rates of 5.0 percent and 5.1 percent, respectively.

Additional exploratory efficacy end points, including length of mechanical ventilation, intensive care unit and hospital stay, and quality of life, did not reach statistical significance.

"These findings illustrate inherent risks of using promising meta-analysis results to plan 'confirmatory' clinical trials. There are several potential explanations for the negative results we observed. One consideration is the decision around study eligibility criteria and the overall primary end point of the trial," the authors write. They add that the lack of benefit of acadesine may be related to the dosing regimen used.

The researchers conclude that the incidence of the primary composite end point of 5 percent indicates the need for continued investigation into therapies to reduce perioperative morbidity and mortality. "However, effective therapies remain elusive."

Explore further: Drug fails to curb heart bypass complications, but surgery gets safer

More information: JAMA. 2012;308[2]:157-164

Related Stories

Drug fails to curb heart bypass complications, but surgery gets safer

July 10, 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, prospective study lead by ...

CABG still preferred over PCI in patients with triple vessel disease

August 29, 2011
Results from CREDO-Kyoto PCI/CABG Registry Cohort-2 show that percutaneous coronary intervention (PCI) was associated with significantly higher risk for serious adverse events in patients with triple vessel disease than coronary ...

Largest study of on-pump and off-pump bypass proves both can be done safely

March 26, 2012
A large randomized trial comparing bypass surgery done with a heart-lung machine (on pump) and without it (off pump) found no differences in results between techniques overall but some clinically relevant differences, according ...

Study finds aggressive glycemic control in diabetic cabg patients does not improve survival

September 27, 2011
Surgeons from Boston Medical Center (BMC) have found that in diabetic patients undergoing coronary artery bypass graft (CABG) surgery, aggressive glycemic control does not result in any significant improvement of clinical ...

Recommended for you

Early study shows shoe attachment can help stroke patients improve their gait

December 14, 2017
A new device created at the University of South Florida – and including a cross-disciplinary team of experts from USF engineering, physical therapy and neurology – is showing early promise for helping correct the signature ...

Scientists rewrite our understanding of how arteries mend

December 13, 2017
Scientists from The University of Manchester have discovered how the severity of trauma to arterial blood vessels governs how the body repairs itself.

Deadly heart rhythm halted by noninvasive radiation therapy

December 13, 2017
Radiation therapy often is used to treat cancer patients. Now, doctors at Washington University School of Medicine in St. Louis have shown that radiation therapy—aimed directly at the heart—can be used to treat patients ...

Ultra-thin tissue samples could help to understand and treat heart disease

December 12, 2017
A new method for preparing ultra-thin slices of heart tissue in the lab could help scientists to study how cells behave inside a beating heart.

Young diabetics could have seven times higher risk for sudden cardiac death

December 12, 2017
Young diabetics could have seven times more risk of dying from sudden cardiac arrest than their peers who don't have diabetes, according to new research.

Research reveals how diabetes in pregnancy affects baby's heart

December 12, 2017
Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have discovered how high glucose levels—whether caused by diabetes or other factors—keep heart cells from maturing ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.