Orlando, Fla.—The addition of clopidogrel to aspirin did not lead to a significant reduction in vein graft intimal hyperplasia during the first year after CABG, according to the CASCADE trial presented Monday during the late-breaking clinical trials session at the 2009 American Heart Association conference.
Principal investigator Alexander Kulik, MD, from the University of Ottawa Heart Institute in Ontario, Canada, noted that the long-term effects of CABG are comprised by vein graft disease, and up to 15 percent of vein grafts occlude within one year. Also, he said 60 percent of grafts are patent 10 years after surgery, noting that intimal hyperplasia is the foundation for graft atherosclerosis.
The prospective, multicenter CASCADE (Clopidogrel After Surgery for Coronary Artery DieasE) trial enrolled 113 randomized patients from May 2006 through July 2008 to evaluate whether the addition of clopidogrel to aspirin reduces saphenous vein graft and graft occlusion after CABG.
In his commentary on the trial, Joseph Sabik, MD, from the Cleveland Clinic Foundation, identified saphenous vein grafts as the “Achilles heel” of cardiac bypass surgery.
“We found no significant difference in the amount of vein graft thickening, or the number of blocked bypasses, cardiovascular events or bleeding events for the surgery patients treated with either aspirin and clopidogrel or aspirin alone,” said Kulik, a cardiovascular surgeon at Boca Raton Community Hospital in Florida.
Researchers randomly assigned the patients to one year of 162 mg a day of aspirin plus 75 mg per day of clopidogrel or 162 mg per day of aspirin plus placebo. More than 90 percent of patients in CASCADE were also taking statins.
According to Kulik, the primary outcome was vein graft intimal area by intravascular ultrasound (IVUS), and the secondary outcomes were vein graft patency, major adverse cardiovascular events and bleeding. The study was powered for a 20 percent clinically relevant reduction with clopidogrel.
IVUS was performed on 90 patients, and the researchers found that the vein graft intimal area at one year was 4.1 mm2 for aspirin plus clopidogrel and 4.9 mm2 for aspirin plus placebo. The overall saphenous vein graft patency was 94.3 percent in the investigative arm and 93.2 percent in the aspirin plus placebo arm. The difference was not statistically significant.
“I think the study presents both good news and bad news,” Kulik said. “The good news is that patients and their doctors can expect more than 90 percent of vein grafts to remain open one year after surgery with the use of aspirin and statins.”
However, Kulik said, "it is bad news for the advancement of the cardiac surgery field. It has been more than 10 years since the last advancement in medical therapy for bypass grafts, which was a study showing that statin therapy helps keep vein grafts open.”
Sabik questioned a few aspects of the CASCADE trial, including whether it was adequately powered to detect a difference, and if more patients would have served that purpose. He suggested that maybe the patients needed to be followed longer.
The CASCADE trial was funded by research grants from Physicians’ Services Inc. Foundation, Boston Scientific and the Bristol-Myers Squibb Sanofi Canada Partnership.