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European Heart Journal Advance Access published online on April 12, 2007
European Heart Journal, doi:10.1093/eurheartj/ehm049
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Impact of aspirin with or without clopidogrel on postoperative bleeding and blood transfusion in coronary surgical patients treated prophylactically with a low-dose of aprotinin

Alexandre Ouattara1,*, Hassine Bouzguenda1, Yannick Le Manach1, Philippe Léger1, Anne Mercadier2, Pascal Leprince3, Nicolas Bonnet3, Gilles Montalescot4, Bruno Riou5 and Pierre Coriat1

1 Department of Anaesthesiology and Critical Care, Institute of Cardiology, Pitié-Salpêtrière University Hospital, Assistance Publique-Hôpitaux de Paris, 47 Boulevard de l'Hôpital, Université Pierre et Marie Curie-Paris 6, 75651 Paris Cedex 13, France
2 EFS, Pitié-Salpêtrière University Hospital, Paris, France
3 Department of Thoracic and Cardiovascular Surgery, Institute of Cardiology, Pitié-Salpêtrière University Hospital, Paris, France
4 Department of Cardiology, Institute of Cardiology, Pitié-Salpêtrière University Hospital, Paris, France
5 Department of Emergency Medicine and Surgery, Pitié-Salpêtrière University Hospital, Paris, France

Received 6 May 2006; revised 1 February 2007; accepted 1 March 2007.

* Corresponding author. Tel: +33 1 42 16 22 51; fax: +33 1 42 16 22 69. E-mail address: alexandre.ouattara{at}psl.aphp.fr


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Aims: Aspirin combined with clopidogrel is the treatment of choice for acute coronary syndromes. Although the maintenance of aspirin until surgery does not affect postoperative bleeding after coronary artery bypass graft (CABG) surgery, the latter may be dramatically increased when clopidogrel is continued over a period of 5 days preoperatively.

Methods and results: This prospective observational study included 217 consecutive patients scheduled for first-time CABG. Postoperative bleeding and blood transfusion requirements were compared (equivalence) between patients pretreated during a period of 5 days prior surgery by either aspirin alone (n = 157) or combined with clopidogrel (n = 60). Aprotinin was systematically used in all these patients considered as high risk for bleeding. We found no significant difference between both groups concerning the preoperative characteristics except for unstable angina (33 vs. 19%, P = 0.02) and left main coronary artery stenosis (27 vs. 13% P = 0.02), which were more frequent in patients receiving clopidogrel. The median chest tube output was similar in both groups 24 h postoperatively at 350 mL (95% CI 150–850) vs. 375 mL (95% CI 175–875), and the difference between groups (7%, 95% CI –9 to 22) did not encompass the predetermined margins of equivalence (25%). No significant difference was found on blood transfusion use (38 vs. 38%, P = 0.99). After adjustment by a propensity score, we found that clopidogrel was not associated with an increased risk of excessive bleeding.

Conclusion: In patients undergoing first-time CABG and treated prophylactically with aprotinin, aspirin and clopidogrel may be continued until surgery without increasing postoperative bleeding or transfusion requirements.

Key Words: Antifibrinolytic drug • Transfusion • Clopidogrel • Hemorrhage • Coronary surgery


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
The combination of aspirin with clopidogrel has been shown to reduce ischaemic complications in patients presenting with acute coronary syndrome.1–3 However, the risk of excessive perioperative bleeding when coronary artery bypass grafting (CABG) is chosen in preference to medical treatment has prompted the current American College of Cardiology/American Heart Association guidelines to recommend delaying the use of clopidogrel until after the coronary status is known.4 Although the preoperative use of aspirin alone does not affect postoperative bleeding5 and decreases mortality6 after CABG surgery, its use with clopidogrel may be responsible for increases in postoperative bleeding, blood products requirement, and need for surgical re-exploration, which in turn may cause a further range of complications.7–12 Consequently, most authors7–13 have recommended withdrawal of clopidogrel at least 5 days prior to elective CABG surgery. The potential benefit of preoperative withdrawal of oral antiplatelet agent must be weighed up with the risk of occurrence of serious adverse coronary events.14,15 In addition, it should be noted that most of the studies which have reported increased bleeding with clopidogrel had certain limitations. The distribution of the antiplatelet therapy was unequal,7 and intraoperative antifibrinolytic therapy was not standardized8,10 or even not used.7 However, the prophylactic use of aprotinin has been reported as an effective intraoperative strategy to decrease bleeding after CABG in patients treated with antiplatelet therapy.16–19 Therefore, we performed a prospective study to compare the effect of preoperative use of aspirin with or without clopidogrel on postoperative bleeding and transfusion requirement in patients undergoing first-time CABG surgery and in whom a standardized intraoperative antifibrinolytic therapy based on aprotinin was systematically used.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusion
 Acknowledgements
 References
 
Selection of patients
This prospective observational study was conducted at the Institute of Cardiology in the Pitié-Salpêtrière Hospital, Paris, France between November 2003 and May 2004 after approval by our Ethical Committee (Comité de Protection des Personnes se Prêtant à la Recherche Biomédicale, CCPPRB Pitié-Salpêtrière, Paris, France). Although care of patients conformed to standard procedures currently used in our institute, a written informed consent was obtained from each patient. During this 6 month period, all patients undergoing isolated first-time CABG were enrolled in the present study. Patients admitted for emergency procedure, following failed percutaneous transluminal coronary angioplasty and off-pump coronary surgery, were excluded. Because antithrombotic therapy was different during the postoperative period, we excluded also patients in whom a mechanical support or intra-aortic balloon pump was required for a difficult weaning from cardiopulmonary bypass. Finally, we excluded all patients who had not received any oral antiplatelet agents within 5 days prior surgery, those who have been preoperatively exposed to platelet glycoprotein IIb/IIIa inhibitors, and those with history of haematological disease. Patients treated with aspirin and in whom clopidogrel was stopped more than 5 days before surgery were included in the aspirin alone group; 217 remaining patients were treated either by aspirin alone (n = 157) or by aspirin and clopidogrel (n = 60) within 5 days prior the surgery (Figure 1). Preoperative patient characteristics as well as intraoperative variables were collected prospectively into a database for later analysis.


Figure 1
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  		Figure 1 Flowchart of the study. IABP, intra-aortic balloon pump; ECMO, extracorporeal membrane oxygenator.

 
Intraoperative management
The standard haemodynamic monitoring included arterial and central venous catheterizations for invasive arterial and central venous pressures monitoring, respectively. Because all patients enrolled in the present study received at least one antiplatelet agent, they were considered at high risk for postoperative bleeding. Consequently, aprotinin (Trasylol, Bayer Pharma, Puteaux, France) was systematically administered as a low-dose regimen, as previously described.20,21 In the absence of allergic events to a test dose of few drops, one million Kallicreïn inhibitor units (KIU) as a loading dose after induction of anaesthesia and in the pump prime were given. Subsequently, a continuous infusion of 0.25 million KIU/h was maintained until the end of the surgical procedure. Before aortic cannulation, an initial loading dose of heparin was directly administered by the surgeon into the right atrium to obtain a whole-blood-activated clotting time >420 s by using a microcoagulation analyser Hemochron Jr II (International Technidyne Corporation, Edison, NJ, USA). This level was maintained by additional heparin bolus during the extra-corporeal circulation. Non-pulsatile cardiopulmonary bypass was ensured by using a roller pump SIII (Stockert Instrumente GmbH, München, Germany) at a flow of 2.4 L/min/m2. The circuit was primed with 500 mL of sodium bicarbonate 14{per thousand}, 500 mL of mannitol 10%, and 250 mL of crystalloid or colloid. The temperature of systemic perfusion during cardiopulmonary bypass (hypothermia<32°C, mild hypothermia 32–36°C, and normothermia>36°C) was left to the discretion of the attending surgeon and was monitored with an oropharyngeal probe. After discontinuation of the cardiopulmonary bypass, heparin was neutralized by protamin sulfate (0.008–0.01 mg/IU of total heparin dose intraoperatively used). Intraoperative cell salvage was systematically used (Electa, Dideco, Mirandola, Italy). As previously reported,22 the blood from the site of operation and the remaining blood in the circuit at the end of the cardiopulmonary bypass was washed, centrifuged, and retransfused into the patient. The use of inotropes for difficult weaning from cardiopulmonary bypass was left to the discretion of the attending anaesthesiologist.

Postoperative antithrombotic therapy
The early postoperative antithrombotic therapy was based on continuous infusion of pentoxyfillin (50 mg/h) started on the arrival in the intensive care unit and intravenous bolus of 100 mg aspirin given 6 h after the arrival in intensive care unit, as previously recommended.23,24 These two drugs were given by mouth as soon as possible. The day after surgery, enoxaparin 40 mg was subcutaneously given once daily. The perioperative blood transfusion was left to the discretion of the attending anaesthesiologist and according to the French National recommendations.25 In patients preoperatively treated by combined antiplatelet therapy, clopidogrel was re-introduced the day after the surgery. Patients initially on single-aspirin therapy were left on aspirin alone after the surgery.

Endpoints
The primary outcome was the chest blood output during the first 24 h, which was estimated to be ~400 ± 200 mL after CABG.26 Excessive bleeding was defined by an increment of at least 25% of this basal value, i.e.>500 mL. Secondary outcomes were the rate of re-exploration for excessive bleeding, transfusion requirement, prolonged mechanical ventilation (>10 h), and intensive care unit length of stay (>72 h).

Statistical analysis
Assuming an alpha risk of 0.05 and a beta risk of 0.20 and a mean amount of postoperative bleeding after CABG in the aspirin-alone group of 400 ± 200 mL, we calculated that at least 70 patients in each group were required to demonstrate that the amount of bleeding in the aspirin-alone group was not 25% less than that of the clopidogrel plus aspirin group (equivalence). Because the ratio between aspirin-alone and clopidogrel plus aspirin groups was estimated to be one-third and taken into account the inequal size for the power calculation, we estimated that at least 188 patients should be included in our study. Lastly, because 5% of our patients did not receive aspirin or clopidogrel, the final number of patients screened was estimated to be 198 and thus the predicted duration of inclusion was 30 weeks.

Categorical variables were compared using Fisher's exact test. Continuous variables were compared using the Mann–Witney U test. The postoperative haemoglobin levels and platelets counts were compared using analysis of variance for repeated measurements completed using a Newman–Keuls test for post-test analysis.

Since this study was not randomized, the patients receiving clopidogrel preoperatively may not have the same perioperative risk of excessive bleeding than those who did not. Therefore, we performed separate multivariable risk adjustment to analyse the perioperative risk associated with clopidogrel treatment. For each patient, a propensity score, indicating the likelihood of having clopidogrel, was calculated.27 The propensity score-matched analysis allowed us to determine whether preoperative clopidogrel therapy was independently associated with an increased risk of excessive postoperative bleeding. All preoperative variables as well as second-order interaction terms have been entered into the model. Calibration and discrimination of the final logistic model were assessed using the Hosmer–Lemeshow statistics and the receiver operating characteristic curve, respectively. Comparison of mean bleeding between several groups (according to propensity score quintiles) was performed using analysis of variance.

Data are expressed as mean ± SD, median, and 5th–95th percentiles or percentage of patients as specified. All P-values were two-tailed and a value less than 0.05 was required to reject the null hypothesis. All analyses were performed with the use of SPSS 13.0 (Chicago, IL, USA).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusion
 Acknowledgements
 References
 
There was no significant difference between the two groups concerning preoperative clinical variables (Table 1) except for a higher prevalence of unstable angina (33 vs. 19% P = 0.02) and left main artery stenosis (27 vs. 13% P = 0.02) in patients treated with clopidogrel. Similarly, the platelet count and plasma creatinin level were significantly lower in patients receiving combined antiplatelet therapy (Table 2). Eight patients in the aspirin group were preoperatively treated with clopidogrel, which was stopped at a median time of 15 days prior the surgery (range 6–23). In patients treated with combined antiplatelet therapy, 92% of them received both oral antiplatelet agents within 2 days before the surgery. The intraoperative characteristics of patients included in the study are summarized in Table 3. Because no patient exhibited an allergic reaction to a test dose, all patients were treated intraoperatively by aprotinin. We found no significant differences in bypass time, cross-clamping time, temperature of systemic perfusion, and the number of internal mammary arteries used between groups (Table 3).


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  		Table 1 Baseline characteristics of patients

 

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  		Table 2 Preoperative biologic variables of patients

 

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  		Table 3 Intraoperative characteristics of patients

 
The main endpoint, the median chest tube output (Figure 2), was similar in both groups 24 h postoperatively at 350 mL (95% CI 150–850) vs. 375 mL (95% CI 175–875). The mean difference in this amount between the two groups was 25 mL corresponding to a 7% difference (95% CI –9 to 22), and this confidence interval did not encompass the predetermined margins of equivalence (25%). An excessive bleeding was observed in 37 (24%) patients in aspirin group vs. 17 (28%) patients in clopidogrel group (P = 0.49). The rate of transfusion and blood products consumption were comparable between groups (Table 4). The re-exploration rate for excessive postoperative bleeding was not significantly different between groups (0 vs. 1%, P = 0.38). There was no significant difference for platelets count and haemoglobin level during the first 24 h (Figure 3A and B). The incidence of prolonged mechanical ventilation (>10 h) was similar in both groups (26 vs. 20%, P = 0.35). Similarly, the percentage of patients requiring prolonged intensive care unit length of stay (>72 h) was not significantly different between both groups (9 vs. 10%, P = 0.80).


Figure 2
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  		Figure 2 Postoperative cumulative chest tube output over the first 24 h in patients treated preoperatively by aspirin alone (n = 157) and aspirin with clopidogrel (n = 60). Lines within boxes represent median values. Upper and lower lines of boxes represent 25th and 75th percentiles, respectively. Upper and lower bars outsides of boxes represent 95th and 5th percentiles, respectively.

 

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  		Table 4 Intraoperative characteristics of patients

 

Figure 3
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  		Figure 3 Postoperative haemoglobin level (panel A) and platelets count (panel B) during the first 24 h in patients treated preoperatively by aspirin alone (n = 157) and aspirin with clopidogrel (n = 60). Data are presented as the mean ± SD.

 
The final model of the propensity score included 21 preoperative variables and the interaction terms. The Hosmer–Lemeshow statistics associated with this model was 3.2 (df 8; P = 0.92) and the c-statistics of the model was 0.95. The adjusted relative risk values of all the variables according to the propensity score are given in Tables 1–4. After propensity score adjustment (Table 5), the preoperative use of clopidogrel was not found to be associated with excessive bleeding (adjusted odds ratio 1.2; 95% CI 0.5–3.4; P = 0.66).


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  		Table 5 Distribution of the propensity score by quintiles according to the clopidogrel therapy

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusion
 Acknowledgements
 References
 
The main finding of the present study is that, in patients undergoing first-time CABG surgery and intraoperatively treated by a half-dose aprotinin regimen, aspirin combined with clopidogrel may be continued up to the day of surgery without increasing postoperative bleeding and transfusion rates.

Aspirin has been shown to improve cardiovascular outcome in patients with coronary artery disease. A multicentre control study demonstrated that cardiac surgical patients preoperatively treated with aspirin have a lower mortality rate.6 Since the use of aprotinin leads to a decrease in blood loss after CABG in patients preoperatively treated by aspirin,16,28 the latter could be safely maintained till the day of the surgery.13 The combination of aspirin with thienopyridines exerts a synergistic inhibition of platelet aggregation and has been associated with a superior protection against ischaemic complications in patients presenting with acute coronary syndromes and/or undergoing stenting.2,3

Thienopyridines irreversibly inhibit ADP-induced platelet aggregation and ADP-mediated amplification of other platelet agonists by selectively binding to adenylate cyclase-coupled ADP receptors on the platelet surface. Among thienopyridines, clopidogrel appears to offer several advantages. It acts much more rapidly and has a lower incidence of adverse effects. Some patients suffering from coronary artery disease cannot be effectively treated by angioplasty and thus, must undergo surgical myocardial revascularization. Consequently, an increasing number of patients undergoing CABG surgery are pretreated with combined antiplatelet therapy including clopidogrel as recommended by European Society of Cardiology Guidelines for acute coronary syndromes.2,7,29 Because the preoperative use of clopidogrel increases both postoperative bleeding and transfusion requirement, several authors have recommended discontinuing clopidogrel for at least 5 days prior to CABG surgery.2,4,7–10,12,30,31 As recently reported by Collet et al.,14 the withdrawal of an antiplatelet agent may be deleterious, especially when a stent has been implanted. Moreover, most of the studies which reported increased blood loss in patients receiving clopidogrel before CABG surgery present some limitations. First, the antiplatelet therapy was unequally distributed among groups studied.7 Secondly, in some studies, the antifibrinolytic therapy was not specified7 or was unequally used.8,10 However, aprotinin, a serine protease inhibitor, has been demonstrated as an effective intraoperative strategy to limit postoperative bleeding in patients undergoing CABG and treated with aspirin,16,28,32 and more recently, with clopidogrel.17,18 Its beneficial effects on the blood loss are related to a decrease in fibrinolysis and platelet dysfunction via an inhibition of plasmin activity.33 In our study, no significant difference was observed between two groups except for a higher prevalence of acute coronary syndromes and left main artery stenosis in patients pretreated by combined antiplatelet therapy. Indeed, since these patients are likely to be at high risk of thrombotic complications, they received a more potent antiplatelet therapy.34 In the present study, we chose to evaluate the impact of combined antiplatelet therapy not discontinued 5 days prior surgery. Because clopidogrel affects platelet function irreversibly, its effect lasts the lifetime of the platelets, ~10 days. In consequence, after discontinuation of treatment by clopidogrel, platelet aggregation progressively returns to baseline value up to 8 days. It is routinely recommended to discontinue clopidogrel at least 5 days prior elective CABG.13 In our study, we found that combining aspirin with clopidogrel did not increase postoperative bleeding in comparison with aspirin alone when patients were treated prophylactically with low-dose aprotinin regimen. Our findings are consistent with those reported by other studies using similar intraoperative strategies to limit blood loss in patients preoperatively treated with clopidogrel.17–19,35 However, it must be pointed out that this intraoperative strategy should be limited to patients with an increased risk of bleeding (i.e. preoperative antiplatelet therapy). Indeed, a recent large observational study reported that intraoperative use of aprotinin could be associated with adverse renal events in patients mostly perioperatively untreated by antiplatelet therapy before CABG.36 Although the present study was not designed for this outcome, the re-exploration rate was comparable in both groups. Because this outcome was rare, a larger number of patients should be included to draw definite conclusion on this endpoint.

The following limitations have to be considered in the assessment of the clinical relevance of our study. First, the present study was purely observational and thus, surgeons were not blinded to the antiplatelet therapy and the hypothesis that they attempted to optimize haemostasis when dual antiplatelet therapy was used cannot be completely ruled out. Secondly, we did not evaluate platelet function. Consequently, the inter-individual variability in the antiplatelet therapy was not taken into account.37,38 Lastly, since this study was not randomized, hidden biases cannot be completely ruled out, although the risk adjustment techniques used in our study limited this possibility.


   Conclusion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
Acknowledgements
 References
 
In patients scheduled for first-time CABG surgery, the discontinuation of clopidogrel 5 days prior the surgery, as previously recommended, does not seem strictly to be required if the patient is intraoperatively treated by low-dose of aprotinin. These results are important since the maintenance of combined antiplatelet therapy till the surgery may allow avoiding adverse coronary events before surgery.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
References
 
We thank Dr David Baker, DM, FRCA (Staff Anaesthesiologist, Department of Anesthesiology, CHU Necker-Enfants Malades, Paris) for reviewing the manuscript. This academic study was supported by the Department of Anaesthesiology and the Department of Cardiovascular Surgery, Centre Hospitalier Universitaire (CHU) Pitié-Salpêtrière.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Acknowledgements
 References
 

  1. Fox KAA, Mehta SR, Peters R, Zhao F, Lakkis N, Gersh BJ, Yusuf S. (2004) Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome. The clopidogrel in unstable angina to prevent recurrent ischaemic events (CURE) trial. Circulation 110:1202–1208.[Abstract/Free Full Text]
  2. The clopidogrel in unstable angina to prevent recurrent ischaemic events trials investigators. (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345:494–502.[Abstract/Free Full Text]
  3. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA. Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. (2001) Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-cure study. Lancet 358:527–533.[CrossRef][Web of Science][Medline]
  4. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE III, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC Jr. American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). (2002) ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: summary article: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on the management of patients with unstable angina). Circulation 106:1893–1900.[Free Full Text]
  5. Tuman KJ, McCarthy RJ, O'Connor CJ, McCarthy WE, Ivankovich AD. (1996) Aspirin does not increase allogenic blood transfusion in reoperative coronary artery surgery. Anesth Analg 83:1178–1184.[Abstract]
  6. Dacey LJ, Munoz JJ, Johnson ER, Leavitt BJ, Maloney CT, Morton JR, Olmstead EM, Birkmeyer JD, O'Connor GT. Northern New England Cardiovascular Disease Study Group. (2000) Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients. Ann Thorac Surg 70:1986–1990.[Abstract/Free Full Text]
  7. Hongo RH, Ley J, Dick SE, Yee RR. (2002) The effect of clopidogrel in combination with aspirin when given before coronary artery bypass grafting. J Am Coll Cardiol 40:231–237.[Abstract/Free Full Text]
  8. Chu MWA, Wilson SR, Novick RJ, Stitt LW, Quantz MKA. (2004) Does clopidogrel increase blood loss following coronary artery bypass surgery? Ann Thorac Surg 78:1536–1541.[Abstract/Free Full Text]
  9. Chen L, Bracey AW, Radovancevic R, Cooper JR, Collard CD, Vaughn WK, Nussmeier NA. (2004) Clopidogrel and bleeding in patients undergoing elective artery bypass grafting. J Thorac Cardiovasc Surg 128:425–431.[Abstract/Free Full Text]
  10. Yende S and Wunderink RG. (2001) Effect of clopidogrel on bleeding after coronary artery bypass surgery. Crit Care Med 29:2271–2275.[CrossRef][Web of Science][Medline]
  11. Gansera B, Schmidtler F, Spiliopoulos K, Angelis I, Neumaier-Prauser P, Kemkes BM. (2003) Urgent or emergent coronary revasularization using bilateral internal thoracic artery after previous clopidogrel antiplatelet therapy. Thorac Cardiovasc Surg 51:185–189.[CrossRef][Web of Science][Medline]
  12. Leong JY, Baker RA, Shah PJ, Cherian VK, Knight JL. (2005) Clopidogrel and bleeding after coronary artery bypass graft surgery. Ann Thorac Surg 80:928–933.[Abstract/Free Full Text]
  13. Cannon CP, Mehta SR, Aranki SF. (2005) Balancing the benefit and risk of oral antiplatelet agents in coronary artery bypass surgery. Ann Thorac Surg 80:768–779.[Abstract/Free Full Text]
  14. Collet JP, Montalescot G, Blanchet B, Tanguy ML, Golmard JL, Choussat R, Beygui F, Payot L, Vignolles N, Metzger JP. (2004) Impact of prior use or recent withdrawal of oral antiplatelet agents on acute coronary syndromes. Circulation 110:2361–2367.[Abstract/Free Full Text]
  15. Ferrari E, Benhamou M, Cerboni P, Marcel B. (2005) Coronary syndromes following aspirin withdrawal. A special risk for late stent thrombosis. J Am Coll Cardiol 45:456–459.[Abstract/Free Full Text]
  16. Murkin JM, Lux J, Shannon NA, Guiraudon GM, Menkis AH, McKenzie FN, Novick RJ. (1994) Aprotinin significantly decreases bleeding and transfusion requirements in patients receiving aspirin and undergoing cardiac operations. J Thorac Cardiovasc Surg 107:554–561.[Abstract/Free Full Text]
  17. Lindvall G, Sartipy U, Van der Linden J. (2005) Aprotinin reduces bleeding and blood product use in patients treated with clopidogrel before coronary artery bypass grafting. Ann Thorac Surg 80:922–927.[Abstract/Free Full Text]
  18. Akowuah E, Shrivastava V, Jamnadas B, Hopkinson D, Sarkar P, Storey R, Braidley P, Cooper G. (2005) Comparison of two strategies for the management of antiplatetlet therapy during urgent surgery. Ann Thorac Surg 80:149–152.[Abstract/Free Full Text]
  19. Van der Linden J, Lindvall G, Sartipy U. (2005) Aprotinin decreases postoperative bleeding and number of transfusions in patients on clopidogrel undergoing coronary artery bypass graft surgery: a double-blind, placebo-controlled, randomized clinical trial. Circulation 112:I276–I280.[CrossRef][Medline]
  20. Levy JH, Pifarre R, Schaff HV, Horrow JC, Albus R, Spiess B, Rosengart TK, Murray J, Clark RE, Smith P, Nadel A, Bonney SL, Kleinfield R. (1995) A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary bypass grafting. Circulation 92:2236–2244.[Abstract/Free Full Text]
  21. Lemmer JH, Dilling EW, Morton JR, Rich JB, Robicsek F, Bricker DL, Hantler CB, Whitten CW, Noon GP, Maddi R. (1996) Aprotinin for primary coronary artery bypass grafting: a multicenter trial of three dose regimens. Ann Thorac Surg 62:1659–1668.[Abstract/Free Full Text]
  22. McGill N, O'Shaughnessy D, Pickering R, Herbertson M, Gill R. (2002) Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial. Br Med J 324:1299–1306.[Abstract/Free Full Text]
  23. Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, Hart JC, Herrmann HC, Hillis LD, Hutter AM Jr, Lytle BW, Marlow RA, Nugent WC, Orszulak TA. American College of Cardiology. (2004) American Heart Association. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation 110:340–437.
  24. Stein PD, Dalen JE, Goldman S, Theroux P. (2001) Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts. Chest 119:278S–282S.[CrossRef][Web of Science][Medline]
  25. Agence Française de Securite Sanitaire des Produits de Sante (AFSSAPS). (2002) Transfusion of erythrocytes substitutes: products, indications, alternatives. General methods and recommendations. Transfus Clin Biol 9:333–356.[CrossRef][Web of Science][Medline]
  26. Ouattara A, Niculescu M, Boccara G, Landi M, Vaissier E, Leger P, Riou B, Gandjbakch I, Coriat P. (2003) Identification of risk factors for allogenic transfusion in cardiac surgery from an observational study. Ann Fr Anesth Réanim 22:278–283.[CrossRef][Web of Science][Medline]
  27. Joffe MM and Rosenbaum PR. (1999) Invited commentary: propensity scores. Am J Epidemiol 100:1043–1049.
  28. Bidstrup BP, Hunt BJ, Sheikh S, Parratt RN, Bidstrup JM, Sapsford RN. (2000) Amelioration of the bleeding tendency of preoperative aspirin after aortocoronary bypass grafting. Ann Throrac Surg 69:541–547.[CrossRef]
  29. Patrono C, Bachmann F, Baigent C, Bode C, De Caterina R, Charbonnier B, Fitzgerald D, Hirsh J, Husted S, Kvasnicka J, Montalescot G, Garcia Rodriguez LA, Verheugt F, Vermylen J, Wallentin L, Priori SG, Alonso Garcia MA, Blanc JJ, Budaj A, Cowie M, Dean V, Deckers J, Fernandez Burgos E, Lekakis J, Lindahl B, Mazzotta G, Morais J, Oto A, Smiseth OA, Morais J, Deckers J, Ferreira R, Mazzotta G, Steg PG, Teixeira F, Wilcox R. European Society of Cardiology. (2004) Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology. Eur Heart J 25:166–181.[Free Full Text]
  30. Englberger L, Faeh B, Berdat PA, Eberli F, Meier B, Carrel T. (2004) Impact of clopidogrel in coronary artery bypass grafting. Eur J Cardiothorac Surg 26:96–101.[Abstract/Free Full Text]
  31. Genoni M, Tavakoli R, Hofer C, Bertel O, Turina M. (2003) Clopidogrel before urgent coronary artery bypass graft. J Thorac Cardiovasc Surg 126:288–289.[Free Full Text]
  32. Ivert T, Intonti M, Stain-Malmgren R, Dumitrescu A, Blombläck M. (1998) Effects of aprotinin during cardiopulmonary bypass in patients treated with acetylsalicyclic acid. Scand Cardiovasc J 32:289–295.[CrossRef][Web of Science][Medline]
  33. van Oeveren W, Harder MP, Roozendaal KJ, Eijsman L, Wildevuur CR. (1990) Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg 99:788–797.[Abstract]
  34. Bhatt DL and Topol EJ. (2004) Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA). Am Heart J 148:263–268.[CrossRef][Web of Science][Medline]
  35. Karabulut H, Toraman F, Evrenkaya S, Goksel O, Tarcan S, Alhan C. (2004) Clopidogrel does not increase bleeding and allogenic blood transfusion in coronary artery surgery. Eur J Cardiothorac Surg 25:419–231.[Abstract/Free Full Text]
  36. Mangano DT, Tudor IC, Dietzel C. (2006) The risk associated with aprotinin in cardiac surgery. N Engl J Med 354:353–365.[Abstract/Free Full Text]
  37. Nguyen TA, Diodati JG, Pharand C. (2005) Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol 45:1157–1641.[Abstract/Free Full Text]
  38. Agarwal S, Coakely M, Reddy K, Riddell A, Mallett S. (2006) Quantifying the effect antiplatelet therapy. A comparison of the platelet function analyzer (PFA-100) and modified thromboelastography (mTEG) with light transmission platelet aggregometry. Anesthesiology 105:676–683.[CrossRef][Web of Science][Medline]

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M. E. Bertrand
When and how to discontinue antiplatelet therapy
Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A35 - A41.
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