NEW YORK (Reuters Health) – In a pilot study of patients undergoing on-pump coronary artery bypass grafting (CABG), adding clopidogrel to aspirin did not reduce overall graft occlusion, Canadian investigators report.
Dual antiplatelet treatment did lower rates of radial artery graft occlusion, according to the report in December issue of the American Heart Journal, but radial arteries made up a small proportion of graft tissue.
Still, the drug combo did not increase blood loss, cardiovascular events or death, so the research team concludes that a large randomized trial comparing the efficacy of clopidogrel/aspirin treatment with aspirin alone after CABG “appears safe and feasible.”
The research team at McMaster University in Hamilton followed 99 patients who underwent on-pump CABG. They randomized 49 patients to clopidogrel (a 300-mg postoperative loading dose followed by 75 mg daily doses for at least 30 days) and 50 to placebo. All patients received aspirin (325 mg loading dose then 81 mg once a day indefinitely).
Roughly 60% opf the grafts were from saphenous veins. Radial arteries were used in 16 grafts in the placebo group and 20 in the clopidogrel group, based on surgeon’s choice.
Lead researcher Dr. Jack C. J. Sun and colleagues evaluated graft patency by CT angiography performed at a median time of 50 days after surgery in 80 patients. They saw no significant difference in the total number of occluded grafts in the placebo group (11/154, 7.1%) and in the clopidogrel group (8/161, 5.0%). The numbers of patients with one or more occluded grafts were also similar in the two groups (9/39, 23.1% vs 7/40, 17.5%), respectively.
However, significantly more occlusions or string signs occurred with placebo compared with clopidogrel (43.8% vs 10.0%, p = 0.03). The number of patients affected was also higher in the placebo group (43.8% vs 10.5%, p = 0.05).
According to Dr. Sun and associates, the rate of radial graft occlusion in the placebo group was substantially higher than has been reported in the literature. Also, “the apparent benefits of clopidogrel compared with placebo on radial graft patency is based on a post hoc analysis and is unexpected because the study was designed to assess feasibility and was not powered for efficacy.”
After 30 days, no nonfatal myocardial infarctions had occurred. There was one stroke and one death in patients taking clopidogrel, but the difference between groups was not significant.
Clopidogrel did not increase postoperative bleeding, transfusions, or the need for reoperation due to bleeding.
Summing up, the authors say, “”The high rate of graft occlusion after cABG underscores the urgent need for randomized trials to identify more effective treatments to reduce thromboembolic complications after CABG surgery.”
The research was partially supported by a research grant from Bristol-Myers-Squibb Canada, and three of the authors report financial ties to one or more pharmaceutical companies.
Reference:
Randomized trial of aspirin and clopidogrel versus aspirin alone for the prevention of coronary artery bypass graft occlusion: the Preoperative Aspirin and Postoperative Antiplatelets in Coronary Artery Bypass Grafting study
Am Heart J 2010;160:1178-1184.
