Clopidogrel-associated bleeding and related complications in patients undergoing coronary artery bypass grafting

Objective. To determine if clopidogrel use before coronary artery bypass grafting (CABG) is associated with an increase in major bleeding, hemorrhage-related complications, or transfusion requirements. Methods. A structured literature search of English-language articles was conducted by using MEDLINE, EMBASE, and the Cochrane Collaboration Database for the period of January 1, 1990-April 30, 2007. Studies were included if they met the following criteria: randomized controlled trials, prospective observational trials, or retrospective trials; characteristics and outcomes of patients who were exposed to clopidogrel within 7 days before CABG were analyzed; at least 20 patients were enrolled; and reported outcomes were related to transfusion requirements, resource utilization, clinical events, or hemorrhage-related reoperation rates. Patients were considered exposed to clopidogrel if they discontinued the drug within a specified time frame that was designated in each study The rates of the outcomes were compared between those patients exposed and those not exposed to clopidogrel. Results. Twenty-three studies, with data on 3505 patients exposed to clopidogrel before CABG, met the selection criteria. Results suggested that clopidogrel exposure within 7 days before CABG increased the risk of major bleeding and related complications, such as reoperation and blood product transfusions. For other outcomes such as mortality, myocardial infarction, or stroke, the studies' designs lacked statistical power to detect significant differences. In five of the 23 studies, antifibrinolytic therapy with aprotinin was evaluated; in the other studies, aprotinin may have been administered, but it was not discussed in detail. In these studies, the clopidogrel-exposed patients typically had significantly higher chest tube output volumes, reoperation rates due to bleeding, and greater transfusion requirements. Although aprotinin appeared to mitigate hemorrhagic risk, the drug has been temporarily suspended from the market due to safety concerns. Conclusion. Clopidogrel exposure within 7 days before CABG is associated with an increase in major bleeding, hemorrhage-related complications, and transfusion requirements, and leads to potentially greater consumption of health care resources. The overall risks and benefits for each patient should be considered before using the drug.