Impact of Perioperative Use of Clopidogrel on Coronary Bypass Grafting Patients: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

MA Jun ,  XU Weijuan , XU Guiping

Department of Anesthesiology, The Friendship Hospital, Urumqi 830049, China;

Corresponding author：

XU Weijuan, Email: xuweijuan01@163.com

Keywords：

Coronary artery bypass grafting; Clopidogrel; Systematic Review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20130148

Video：

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Objective 　To systematically evaluate impact of perioperative use of clopidogrel on coronary bypass grafting (CABG) patients for anti-platelet treatment, in order to provide evidence for the rational drug use of such patients in the perioperative period.
Methods 　PubMed, EMbase, HighWire, CENTRAL and its affiliated clinical trial registered data center, CBM and CNKI were electronically searched from 2003 to November, 2012. Randomized controlled trials (RCTs) and non-randomized clinical trials on perioperative use of clopidogrel of CABG patients were collected. References of included studies were also retrieved. Two reviewers independently screened studies according to exclusion and inclusion criteria, extracted data, and assessed the methodological quality. Then, meta-analysis was performed using RevMan 5.0 software.
Results 　18 studies (including 10 RCTs and 8 non-randomized clinical trials) involving 14 592 patients were included. The results of meta-analysis showed that: a) Among 10 included RCTs, preoperative use of clopidogrel for anti-platelet treatment reduced the incidence of myocardial infarction obviously, compared with the blank control group (RR=0.63, 95%CI 0.48 to 0.83, P=0.000 9), but there is no significant difference between the two groups in blood loss amount within 24 hours after operation (MD=130, 95%CI –6.21 to 266.22, P=0.06), the number of reoperation patients because of bleeding (RR=1.42, 95%CI 0.92 to 2.20, P=0.12), and risk of postoperative short-term death (RR=1.19, 95%CI 0.89 to 1.58, P=0.24); b) Among 8 non-randomized clinical trials, there was no significant difference between the two groups in reducing the incidence of myocardial infarction (RR=0.83, 95%CI 0.30 to 2.26, P=0.71), but preoperative use of clopidogrel for anti-platelet treatment significantly increased blood loss amount within 24 hours after operation (MD=82.42, 95%CI 35.18 to 129.66, P=0.000 6), the number of reoperation patients because of bleeding (RR=1.71, 95%CI 1.07 to 2.75, P=0.03), and risk of postoperative short-term death (RR=1.89, 95%CI 1.15 to 3.12, P=0.01).
Conclusion 　Current evidence shows that, perioperative use of clopidogrel can reduce the incidence of myocardial infarction, but doctors should consider cautiously the increased risk of bleeding, re-operation and postoperative short-term death. There is contradiction between the results of RCTs and those of non-randomized clinical trials, which may result from the argument intensity, quantity and sample size bias of the included studies. The above conclusion should be proved by large-scale high-quality RCT results in future.

Citation： MA Jun,XU Weijuan,XU Guiping. Impact of Perioperative Use of Clopidogrel on Coronary Bypass Grafting Patients: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2013, 13(7): 827-835. doi: 10.7507/1672-2531.20130148 Copy

1.	Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery:areportof the American College of Cardiology/American Heart Association Task Forceon Practice Guidelines(Committee toUpdate the1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation, 2004, 110: e340-e437.
2.	Despotin GJ, Filos KS, Zoys TN, et al. Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: a multivariate analysis in cardiac surgical patients. Anesth Analg, 1996, 82(1): 13-21.
3.	Alghamdi AA, Moussa F, Fremes SE. Does the use of preoperative aspirin increase the risk of bleeding in patients undergoing coronary artery bypass grafting surgery? Systematic review and meta-analysis. J Card Surg, 2007, 22(3): 247-256.
4.	Gansera B, Schmidtler F, Spiliopoulos K. et al. Urgent or emergent coronary revascularization using bilateral internal thoracic artery after previous clopidogrel antiplatelet therapy. Thorac Cardiovasc Surg, 2003, 51(2): 185-189.
5.	Woo YJ, Grand T, Valettas N. Off-pump coronary artery bypass grafting attenuates postopera- tive bleeding associated with preoperative clopidogrel administration. Heart Surg Forum, 2003, 3(10): 282-285.
6.	Dempsey CM, Lim MS, Stacey SG. A prospective audit of blood loss and blood transfusion in patients undergoing coronary artery bypassgrafting after Clopidogrel and aspirintherapy. Crit Care Resusc, 2004, 6(5): 248-252.
7.	Karabulut H, Toraman F, Evrenkaya S, et al. Clopidogrel does not increase bleeding and allogen -ic blood transfusion in coronary artery surgery. Eur J Cardiothorac Surg, 2004, 25(3): 419-423.
8.	Chen L, Bracey AW, Radovancevic R, et al. Clopidogrel and bleeding in patients undergoing elective coronaryartery bypassgrafting. J Thorac Cardiovasc Surg, 2004, 128(7): 425-431.
9.	Nurozler F, KutluT, Kücük G, et al. Impact of clopidogrel on postoperative blood loss after non-elective coronary bypass surgery. Interact Cardiovasc Thorac Surg, 2005, 4(10): 546-549.
10.	Ascione R, Ghosh A, Rogers CA, et al. In-hospital patients exposed to clopidogrel before corona- ry artery bypass graft surgery: aword of caution. Ann Thorac Surg, 2005, 79(2): 1210-1216.
11.	Leong JY, Baker RA, Shah PJ, et al. Clopidogrel and bleed in gafter coronary artery bypass graft surgery. Ann Thorac Surg, 2005, 80(11): 928-933.
12.	Mehta RH, Roe MT, Mulgund J, et al. Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery. Jam CollCardiol, 2006, 48(7): 281-286.
13.	Kang W, Theman TE, Reed JF, et al. The effect of preoperative clopidogrel on bleeding after coronary artery bypass surgery. J Surg Educ, 2007, 64(10): 88-92.
14.	Filsouﬁ F, Rahmanian PB, Castillo JG, et al.Clopidogrel treatment before coronary artery bypass graft surgery increases postoperative morbidity and blood product requirements. J Cardiothorac Vasc Anesth, 2008, 22(1): 60-66.
15.	Kim JH, Newby LK, Clare RM, et al. Clopidogrel use and bleeding after coronary artery bypass graft surgery. Am Heart J, 2008, 156(4): 886-892.
16.	Maltais S, Perrault LP, Do QB. Effect of clopidogrel on bleeding and transfusions after off- pump coronary artery bypass graft surgery: impact of discontinuation prior to surgery. Eur J Cardiothorac Surg, 2008, 34(5): 127-131.
17.	Ebrahimi R, Dyke C, Mehran R, et al. Outcomes following pre-operative clopidogrel administra -tion in patients with acute coronary syndromes undergoing coronaryartery bypass surgery: the ACUITY(Acute Catheterization and Urgent Intervention Triagestrateg Y)trial. J Am Coll Cardiol, 2009, 53(2): 1965-1972.
18.	Vaccarino GN, Thierer J, Albertal M, et al. Impact of preoperative clopidogrel in offpump coronary artery bypass surgery: apropensityscore analysis. J Thorac Cardiovasc Surg, 2009, 137(4): 309-313.
19.	Nesher N, Singh SK, Hosam F, et al. Impact of clopidogrel use on mortality and major bleeding in patients undergoing coronary artery bypass surgery. Interactive Cardio Vascular and Thoracic Surgery, 2010, 10(8): 732-736.
20.	Mengistu AM, Mayer J, Boldt J, et al. Usefulness of monitoring platelet function by multiple electrode aggregometry in primary coronary artery bypass surgery. J Cardiothorac Vasc Anesth, 2011, 25(3): 42-47.
21.	Hartmuth B. Bittner, Sven L, et al. Impact of clopidogrel on bleeding complications and survival in off-pump coronary artery bypass grafting. Interactive Cardio Vascular and Thoracic Surgery, 2012, 14(2): 273-278.
22.	Daly DJ, Myles PS, Smith JA, et al. Anticoagulation, bleeding and blood transfusion practices in Australasian cardiac surgical practice.Anaesth Intensive Care, 2007, 35(5): 760-768.
23.	王禹, 盖鲁粤, 沈洪, 等. 国产氯吡格雷在急性心肌梗死急诊冠脉介人治疗过程中的有效性及对血小板聚集功能的影响. 中国急救医学, 2006, 26(7): 512-514.
24.	Ranucci M, Bozzetti G, Ditta A, et al. Surgical re-exploration after cardiac operations:why aworse outcome?. Ann ThoracSurg, 2008, 86(8): 1557-1562.
25.	马海平, 郑宏. 抗血小板治疗冠状旁路移植术围术期抗纤溶治疗效果的荟萃分析. 中华心血管病杂志, 2011, 39 (8): 759-763.

1. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery:areportof the American College of Cardiology/American Heart Association Task Forceon Practice Guidelines(Committee toUpdate the1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation, 2004, 110: e340-e437.
2. Despotin GJ, Filos KS, Zoys TN, et al. Factors associated with excessive postoperative blood loss and hemostatic transfusion requirements: a multivariate analysis in cardiac surgical patients. Anesth Analg, 1996, 82(1): 13-21.
3. Alghamdi AA, Moussa F, Fremes SE. Does the use of preoperative aspirin increase the risk of bleeding in patients undergoing coronary artery bypass grafting surgery? Systematic review and meta-analysis. J Card Surg, 2007, 22(3): 247-256.
4. Gansera B, Schmidtler F, Spiliopoulos K. et al. Urgent or emergent coronary revascularization using bilateral internal thoracic artery after previous clopidogrel antiplatelet therapy. Thorac Cardiovasc Surg, 2003, 51(2): 185-189.
5. Woo YJ, Grand T, Valettas N. Off-pump coronary artery bypass grafting attenuates postopera- tive bleeding associated with preoperative clopidogrel administration. Heart Surg Forum, 2003, 3(10): 282-285.
6. Dempsey CM, Lim MS, Stacey SG. A prospective audit of blood loss and blood transfusion in patients undergoing coronary artery bypassgrafting after Clopidogrel and aspirintherapy. Crit Care Resusc, 2004, 6(5): 248-252.
7. Karabulut H, Toraman F, Evrenkaya S, et al. Clopidogrel does not increase bleeding and allogen -ic blood transfusion in coronary artery surgery. Eur J Cardiothorac Surg, 2004, 25(3): 419-423.
8. Chen L, Bracey AW, Radovancevic R, et al. Clopidogrel and bleeding in patients undergoing elective coronaryartery bypassgrafting. J Thorac Cardiovasc Surg, 2004, 128(7): 425-431.
9. Nurozler F, KutluT, Kücük G, et al. Impact of clopidogrel on postoperative blood loss after non-elective coronary bypass surgery. Interact Cardiovasc Thorac Surg, 2005, 4(10): 546-549.
10. Ascione R, Ghosh A, Rogers CA, et al. In-hospital patients exposed to clopidogrel before corona- ry artery bypass graft surgery: aword of caution. Ann Thorac Surg, 2005, 79(2): 1210-1216.
11. Leong JY, Baker RA, Shah PJ, et al. Clopidogrel and bleed in gafter coronary artery bypass graft surgery. Ann Thorac Surg, 2005, 80(11): 928-933.
12. Mehta RH, Roe MT, Mulgund J, et al. Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery. Jam CollCardiol, 2006, 48(7): 281-286.
13. Kang W, Theman TE, Reed JF, et al. The effect of preoperative clopidogrel on bleeding after coronary artery bypass surgery. J Surg Educ, 2007, 64(10): 88-92.
14. Filsouﬁ F, Rahmanian PB, Castillo JG, et al.Clopidogrel treatment before coronary artery bypass graft surgery increases postoperative morbidity and blood product requirements. J Cardiothorac Vasc Anesth, 2008, 22(1): 60-66.
15. Kim JH, Newby LK, Clare RM, et al. Clopidogrel use and bleeding after coronary artery bypass graft surgery. Am Heart J, 2008, 156(4): 886-892.
16. Maltais S, Perrault LP, Do QB. Effect of clopidogrel on bleeding and transfusions after off- pump coronary artery bypass graft surgery: impact of discontinuation prior to surgery. Eur J Cardiothorac Surg, 2008, 34(5): 127-131.
17. Ebrahimi R, Dyke C, Mehran R, et al. Outcomes following pre-operative clopidogrel administra -tion in patients with acute coronary syndromes undergoing coronaryartery bypass surgery: the ACUITY(Acute Catheterization and Urgent Intervention Triagestrateg Y)trial. J Am Coll Cardiol, 2009, 53(2): 1965-1972.
18. Vaccarino GN, Thierer J, Albertal M, et al. Impact of preoperative clopidogrel in offpump coronary artery bypass surgery: apropensityscore analysis. J Thorac Cardiovasc Surg, 2009, 137(4): 309-313.
19. Nesher N, Singh SK, Hosam F, et al. Impact of clopidogrel use on mortality and major bleeding in patients undergoing coronary artery bypass surgery. Interactive Cardio Vascular and Thoracic Surgery, 2010, 10(8): 732-736.
20. Mengistu AM, Mayer J, Boldt J, et al. Usefulness of monitoring platelet function by multiple electrode aggregometry in primary coronary artery bypass surgery. J Cardiothorac Vasc Anesth, 2011, 25(3): 42-47.
21. Hartmuth B. Bittner, Sven L, et al. Impact of clopidogrel on bleeding complications and survival in off-pump coronary artery bypass grafting. Interactive Cardio Vascular and Thoracic Surgery, 2012, 14(2): 273-278.
22. Daly DJ, Myles PS, Smith JA, et al. Anticoagulation, bleeding and blood transfusion practices in Australasian cardiac surgical practice.Anaesth Intensive Care, 2007, 35(5): 760-768.
23. 王禹, 盖鲁粤, 沈洪, 等. 国产氯吡格雷在急性心肌梗死急诊冠脉介人治疗过程中的有效性及对血小板聚集功能的影响. 中国急救医学, 2006, 26(7): 512-514.
24. Ranucci M, Bozzetti G, Ditta A, et al. Surgical re-exploration after cardiac operations:why aworse outcome?. Ann ThoracSurg, 2008, 86(8): 1557-1562.
25. 马海平, 郑宏. 抗血小板治疗冠状旁路移植术围术期抗纤溶治疗效果的荟萃分析. 中华心血管病杂志, 2011, 39 (8): 759-763.

Chinese Journal of Evidence-Based Medicine

Impact of Perioperative Use of Clopidogrel on Coronary Bypass Grafting Patients: A Meta-Analysis

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