Platelet-function Testing May Predict CABG Bleeding in Patients on Clopidogrel

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco. Dr. Boyle reports no financial relationship relevant to this field of study.

Source: Kwak Y-L, et al. Clopidogrel responsiveness regardless of the discontinuation date predicts increased blood loss and transfusion requirement after off-pump coronary artery bypass graft surgery. J Am Coll Cardiol. 2010;56:1994-2002.

Patients taking dual anti-platelet therapy (DAPT) with aspirin and clopidogrel are at higher risk of bleeding with coronary artery bypass graft surgery (CABG) than those taking aspirin alone. Current guidelines recommend ceasing clopidogrel at least 5 days before CABG, but sometimes this is not practical. There is considerable inter-individual variation in clopidogrel metabolism, so waiting for 5 days off clopidogrel may be appropriate for some patients, but may put others at risk of ischemic complications. A more accurate way to assess platelet function and the risk of CABG bleeding in these patients has the potential to make the peri-operative period safer. Kwak and colleagues prospectively enrolled patients undergoing off-pump CABG (OPCABG) who were previously on clopidogrel into their registry. They recorded the duration since clopidogrel cessation, and also performed platelet thromboelastography (TEG) as a marker of platelet function to determine when the effects of clopidogrel had worn off. They chose OPCABG to avoid the platelet activation that occurs when blood comes in contact with the cardiopulmonary bypass circuit.

After excluding patients who had emergency surgery, thrombocytopenia, anemia, bleeding diatheses, hepatic or renal dysfunction, prior cardiac surgery, ejection fraction < 40%, myocardial infarction, and those who had received glycoprotein IIb/IIIa inhibitors, the authors enrolled 100 patients undergoing isolated OPCABG. Patients were receiving aspirin 100 mg daily and clopidogrel 75 mg daily for at least a week. To determine the effect of duration of clopidogrel cessation, they were divided into two groups: those receiving aspirin + clopidogrel until 1 day before surgery (n = 50) and those receiving aspirin and clopidogrel until 3 days before surgery (n = 50). To assess outcomes based on the level of platelet inhibition to clopidogrel, TEG was performed immediately before induction of anesthesia, and the surgeon and anesthesiologists were blinded to the results. Patients were grouped according to tertiles of platelet-inhibitory response to clopidogrel.

Results: Baseline demographics were well-matched between groups. Patients with the most platelet inhibition (third tertile) assessed by TEG had the most bleeding and required more blood transfusions postoperatively. Furthermore, these patients also had increased length of stay in the hospital. In multi-variable analysis, the highest platelet inhibition (third tertile) assessed by TEG was the only independent predictor for increased transfusion requirement (odds ratio 10.6; p = 0.001). Interestingly, the duration of discontinuation of clopidogrel prior to surgery was not an independent predictor of transfusion requirement. The optimal cut-off for postoperative transfusion requirement was 70% platelet-inhibitory response to clopidogrel, which provided a sensitivity and specificity of 77.8% and 75.0%, respectively. The platelet response to aspirin did not correlate with bleeding. The authors conclude that a high percentage of platelet-inhibitory response to clopidogrel, regardless of the proximity of clopidogrel exposure, predicts increased blood loss and transfusion requirement after OPCABG, with a cutoff value of 70% for increased risk of transfusion. These findings might implicate a potential role of modified thromboelastography in deciding timing of OPCABG in patients who need continued clopidogrel therapy.

Commentary

The variation in clopidogrel metabolism between patients makes peri-operative management of DAPT difficult. Now, Kwak and colleagues can start to address how we can tailor decisions about surgical timing in individuals, rather than populations. Several limitations of the study should be noted. This study is small and involves a highly selected population. The results may not be generalizable to all CABG surgeries, particularly those performed with cardiopulmonary bypass. The TEG testing for platelet function is not widely available, and the findings may not apply to all types of platelet-function testing. Furthermore, it does not address the risk of ceasing clopidogrel 5-7 days pre-operatively in terms of ischemic complications. We are also not told the reasons for dual antiplatelet therapy in these patients. Those with newly implanted drug-eluting stents are likely at higher risk of ischemic complications than those who were on DAPT for other reasons. However, this study takes an important step toward individualizing patient care for those patients taking DAPT. The finding that assessing the platelet function, rather than just stopping the drug and assuming it has worn off in the expected time frame, can better predict outcomes following OPCABG is very exciting. This could lead to better patient outcomes at reduced cost, but future prospective studies are needed in larger numbers of patients to confirm that tailoring surgical times based on platelet-function studies can reduce bleeding complications.