ATLANTA — The antiplatelet drug clopidogrel is tricky to use in patients undergoing coronary bypass surgery.
Patients who receive clopidogrel immediately before surgery face an increased risk of bleeding and stroke during surgery, an increased need for blood transfusions, and an increased risk of postsurgical death, according to results from previously reported studies, Dr. Frank Shannon said at the annual meeting of the American College of Cardiology.
In a separate poster presentation, Dr. John H. Alexander and his associates reported that patients who received clopidogrel immediately after coronary artery bypass grafting (CABG) surgery had a higher rate of death and graft failure, compared with those who did not receive clopidogrel.
Clopidogrel and aspirin are increasingly being given to patients after CABG because some physicians believe the combination will prevent graft failure and improve patient outcomes. But a post hoc analysis of data collected in a study with more than 3,000 CABG patients suggests that the exact opposite occurs, said Dr. Alexander, a cardiologist at Duke University in Durham, N.C.
The Project of Ex-Vivo Vein Graft Engineering Via Transfection (PREVENT) IV trial was designed to test the efficacy of the experimental drug edifoligide in preventing vein graft failure in 3,014 patients who underwent CABG at 107 centers in the United States; the results were negative. The focus of Dr. Alexander's presentation was the post hoc analysis of the impact of clopidogrel treatment categorized patients on the basis of whether they received clopidogrel between their hospital discharge and 30 days after surgery. Patients who died during the first 30 days were excluded.
In patients who survived past 30 days, 634 received clopidogrel, and 2,327 did not. The use of clopidogrel was entirely at the discretion of the treating physicians and often seemed to be linked to the general policy of individual centers. A few centers prescribed clopidogrel to all or virtually all of their enrolled CABG patients, whereas physicians at several study sites wrote no prescriptions for clopidogrel.
Angiography of the bypass vessels was done 1 year after surgery as part of the study protocol on 1,920 patients. The rate of graft occlusion at 1 year was 40% in patients who did not get clopidogrel and 49% in those who did, a statistically significant difference. The incidence of death, myocardial infarction, or need for revascularization 2 years after surgery was 13.6% in patients who did not receive clopidogrel and 17.3% in patients who did, a statistically significant difference.
In a multivariate analysis that controlled for possible confounders including age, gender, use of cardiopulmonary bypass, duration of surgery, and renal function, use of clopidogrel in the first weeks after CABG was associated with a significant 31% increased risk of graft occlusion and a significant 29% increased risk of death, MI, or need for revascularization. A prospective, randomized trial is needed to definitively assess the effect of clopidogrel treatment after CABG, said Dr. Alexander and his associates in their poster.
Preoperative use of clopidogrel can both cause problems and be of benefit. In a recent study designed to quantify the risk of stopping clopidogrel before CABG, the incidence of MIs after the drug was stopped and before surgery was 12%, compared with no MIs in patients who continued on clopidogrel through most of the preoperative period, said Dr. Frank Shannon, a cardiovascular surgeon at William Beaumont Hospital in Royal Oak, Mich.
But results from other studies have documented that clopidogrel treatment that is continued nearly to the time of surgery boosts the risk of significant intraoperative bleeding, which leads to an increased need for large-volume transfusions and reduced postoperative survival, increased systemic sepsis, and an increased rate of skin infections.