LETTER TO THE EDITOR
Coronary artery bypass graft surgery in patients with recent exposure to clopidogrel and aspirin therapy
Enoch Akowuah, MRCS
Northern General Hospital, Cardiothoracic Surgery, Herries Road, Sheffield, South Yorkshire S5 7AUUnited Kingdom
Vivek Shrivastava, MRCS and
Graham Cooper, FRCS (C/Th)
akowuah{at}yahoo.com
We read with great interest the study by Hongo et al. (1) entitled "The Effect of Clopidogrel in Combination With Aspirin When Given Before Coronary Artery Bypass Grafting." This very interesting study highlights an emerging problem for patients having routine coronary artery bypass graft surgery (CABG) after percutaneous intervention, as described in their report, but also for patients with an acute coronary syndrome who require urgent "in-house surgery" because these patients are invariably on both clopidogrel and aspirin therapy.
In their study, the investigators showed that continued clopidogrel therapy within seven days of elective CABG results in increased blood loss, increased use of blood products, and increased re-exploration rates. Unfortunately, although the study was prospective there was no blinding of the nurses or clinicians to clopidogrel and aspirin exposure.
This lack of blinding is crucial to determine whether the main outcomes of the study are credible. The investigators acknowledged that recording of blood loss may be biased, but so could the decision to use blood and blood products (guidelines for the use of blood and blood products were not stated in their report). Also, no data were provided on the use of antifibrinolytic drugs. Use of drugs like aprotinin and tranexamic acid in patients with a high risk of bleeding is now well established, and this data would be relevant, particularly in patients who underwent re-exploration (2–4). Moreover, although the Society of Thoracic Surgeons’ guidelines for re-exploration were used, these are open to interpretation, and the decision of a surgeon not blinded to clopidogrel therapy may be biased.
In addition, there was no measure of platelet function to demonstrate the fact that platelet aggregation was different between the two groups preoperatively and that this difference persists postoperatively and therefore directly accounts for the difference in postoperative bleeding and other outcome measures used. This is particularly important because the time from last clopidogrel dose to surgery ranged from 0 to 7 days, and in some patients, particularly those in whom clopidogrel therapy was stopped at least 5 days before surgery, other factors may have caused bleeding. In the Clopidogrel in Unstable Angina to prevent Recurrent Ischaemic Events (CURE) trial, patients in whom clopidogrel therapy was halted less than five days before surgery had a trend toward more major bleeding than those on placebo (9.6% vs. 6.3%, p = 0.06), whereas this trend was not seen in patients in whom surgery was performed more than five days after clopidogrel therapy was stopped (5).
In our experience, patients on clopidogrel and aspirin up to the time of surgery can be operated on safely provided a pro-coagulant drug like aprotinin or tranexamic acid is used intraoperatively. As discussed by Hongo et al. (1), antiplatelet therapy that is continued up to the time of surgery may be beneficial; in the case of aspirin it may improve mortality (6), and clopidogrel may reduce platelet activation owing to cardiopulmonary bypass (7,8). Until the question of the role of a pro-coagulant and platelet-protective drug (9) like aprotinin is defined, it is premature to conclude that surgery for patients with a history of clopidogrel exposure within seven days of operation should be delayed.
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References
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1. Hongo RH, Ley J, Dick SE, et al. The effect of clopidogrel in combination with aspirin when given before coronary artery bypass grafting. J Am Coll Cardiol. 2002;40:231–237[Abstract/Free Full Text]
2. Wong BI, McLean RF, Fremes SE, et al. Aprotinin and tranexamic acid for high transfusion risk cardiac surgery. Ann Thorac Surg. 2000;69:808–816[Abstract/Free Full Text]
3. Landymore RW, Murphy JT, Lummis H, et al. The use of low-dose aprotinin,  -aminocaproic acid or tranexamic acid for prevention of mediastinal bleeding in patients receiving aspirin before coronary artery bypass operations. Eur J Cardiothorac Surg. 1997;11:798–800[Abstract]
4. Alverez JM, Jackson LR, Chatwin C, et al. Low-dose postoperative aprotinin reduces mediastinal drainage and blood product use in patients undergoing primary coronary artery bypass grafting who are taking aspirin: a prospective randomised, double-blind placebo-controlled trial. J Thorac Cardiovasc Surg. 2001;122:457–463[Abstract/Free Full Text]
5. Mitka M. Results of CURE trial for acute coronary syndrome. JAMA. 2001;285:1828–1829[Free Full Text]
6. Northern New England Cardiovascular Disease study groupDacey LJ, Munoz JJ, Johnson ER, et al. Effect of preoperative aspirin on mortality in coronary artery bypass grafting patients. Ann Thorac Surg. 2000;70:1986–1990[Abstract/Free Full Text]
7. Tabuchi N, Huet RC, Sturck A, et al. Hemostatic function of aspirin-treated platelets vulnerable to cardiopulmonary bypass. Altered shear-induced pathway. J Thorac Cardiovasc Surg. 1995;110:812–818
8. Taka T, Onkano E, Seki J, et al. Effects of clopidogrel on platelet activation and coagulation on non-anticoagulated rat blood under shear stress. Haemostasis. 1999;29:363–368
9. Poullis M, Manning R, Laffan M, et al. The antithrombotic effect of aprotinin: actions mediated via the protease-activated receptor-1. J Thorac Cardiovasc Surg. 2000;120:370–378[Abstract/Free Full Text]
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