Single High-dose Atorvastatin Loading before Off-pump Coronary Artery Bypass Grafting Alleviates Postoperative Myocardial Injury: A Prospective Randomized Controlled Trial_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANGYang-yang ¹ , WEILei ¹ , XIAYu ² , WANGXiao-wei ¹ , XUXiao-han ¹ , ZHANGWei-ran ¹ ,  CHENYi-jiang ¹

1. Department of Thoracic and Cardiovascular Surgery, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P. R. China;
2. Depar-tment of Thoracic and Cardiovascular Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P. R. China;

Corresponding author：

CHENYi-jiang, Email: YJchen@njmu.edu.cn

Keywords：

Off-pump coronary artery bypass grafting; Myocardial injury; Statin; Randomized controlled trial

DOI：

10.7507/1007-4848.20140207

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Objective To evaluate the safety and myocardial protective results of single high-dose Atorvastatin loading before off-pump coronary artery bypass grafting (OPCAB). Methods A total of 140 patients undergoing selective OPCAB in Jiangsu Province Hospital between February 2010 and August 2011 were recruited in this study. All the patients were randomly divided into a control group and an Atorvastatin loading group (single oral atorvastatin 80 mg)with 70 patients in each group. Biomarkers of cardiac injury including Troponin T (TnT), creatine kinase-MB (CK-MB)and myoglobin (Mb)were measured on admission, 6, 12, 24, 48, 72, 96 and 120 hours after OPCAB. Liver function (alanine aminotransferase (ALT), aspartate aminotransferase (AST)and total bilirubin (TBIL)), serum lipids (total cholesterol (TC), trigl-yceride (TG)and low-density lipoprotein cholesterol (LDL-C))and high-sensitivity C-reactive protein (hsCRP)were measured 2 days before OPCAB, 1, 4 and 7 days after OPCAB as well as before discharge. Results All the patients successfully received OPCAB and were discharged. There was no statistical difference in preoperative clinical characteristics or above indexes between the 2 groups (P > 0.05). There was no statistical difference in ALT or AST between the 2 groups. Incidences of ALT (4.29% vs. 5.71%, P=1.000)and AST (4.29% vs. 0%, P=0.245)greater than 3 times above the upper normal limit were not statistically different between the 2 groups. Peak levels of postoperative TnT (0.23±0.27 ng/ml vs. 0.16±0.24 ng/ml, P=0.011), CK-MB (29.57±30.04 U/L vs. 17.73±14.07 U/L, P=0.001)and hsCRP (31.85±22.89 mg/L vs. 20.81±10.96 mg/L, P=0.001)of the control group were significantly higher than those of Atorvastatin loading group. Incidences of TnT greater than the upper normal limit (47.1% vs. 65.7%, P=0.041)and TnT greater than 5 times above the upper normal limit (8.6% vs. 22.9%, P=0.037)of Atorvastatin loading group were significantly lower than those of the control group. Incidence of CK-MB greater than the upper normal limit of Atorvastatin loading group was significantly lower than that of the control group (20.0% vs. 54.3%, P=0.000). Conclusion Single high-dose Atorvastatin loading before OPCAB is safe and can alleviate postoperative myocardial injury.

Citation： ZHANGYang-yang, WEILei, XIAYu, WANGXiao-wei, XUXiao-han, ZHANGWei-ran, CHENYi-jiang. Single High-dose Atorvastatin Loading before Off-pump Coronary Artery Bypass Grafting Alleviates Postoperative Myocardial Injury: A Prospective Randomized Controlled Trial. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(6): 713-720. doi: 10.7507/1007-4848.20140207 Copy

1.	Kovacević R, Majkić-Singh N, Ignjatović S, et al. Troponin T levels in detection of perioperative myocardial infarction after coronary artery bypass surgery. Clin Lab, 2004, 50(7-8):437-445.
2.	Noora J, Ricci C, Hastings D, et al. Determination of troponin I release after CABG surgery. J Card Surg, 2005, 20(2):129-135.
3.	Ioannidis JP, Karvouni E, Katritis DG. Mortality risk conferred by small elevations of creatine kinase-MB isoenzyme after percutaneous intervention. J Am Coll Cardiol, 2003, 42(8):1406-1411.
4.	Ellis SG, Chew D, Chan A, et al. Death following creatine kinase-MB elevation after coronary intervention:identification of an early risk period:importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy. Circulation, 2002, 106(10):1205-1210.
5.	Klatte K, Chaitman BR, Theroux P, et al. Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release:results from the GUARDIAN trial. J Am Coll Cardiol, 2001, 38(4):1070-1077.
6.	Steuer J, Hörte LG, Lindahl B, et al. Impact of perioperative myocar-dial injury on early and long-term outcome after coronary artery bypass grafting. Eur Heart J, 2002, 23(15):1219-1227.
7.	Herrmann J, Lerman A, Baumgart D, et al. Preprocedural statin medication reduces the extent of periprocedural non-Q-wave myocardial infarction. Circulation, 2002, 106(17):2180-2183.
8.	Pasceri V, Patti G, Nusca A, et al. Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention:results from the ARMYDA(Atorvastatin for Reduction of MYocardial Damage during Angioplasty)study. Circulation, 2004, 110(6):674-678.
9.	Chan AW, Bhatt DL, Chew DP, et al. Relation of inflammation and benefit of statins after percutaneous coronary intervention.Circulation, 2003, 107(13):1750-1756.
10.	Briguori C, Visconti G, Focaccio A, et al. Novel approaches for preventing or limiting events(Naples)II trial:impact of a single high loading dose of atorvastatin on periprocedural myocardial infar-ction. J Am Coll Cardiol, 2009, 54(23):2157-2163.
11.	Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes:the MIRACL study:a randomized controlled trial. JAMA, 2001, 285(13):1711-1718.
12.	Yun KH, Jeong MH, Oh SK, et al. The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients with acute coronary syndrome. Int J Cardiol, 2009, 137(3):246-251.
13.	Christenson JT. Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG. Eur J Cardiothorac Surg, 1999, 15(4):394-400.
14.	Thygesen K, Alpert JS, White HD. Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J, 2007, 28(20):2525-2538.
15.	Desager JP, Horsmans Y.Clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors.Clin Pharmacokinet, 1996, 31(5):348-371.
16.	Erkelens DW. Combination drug therapy with HMG CoA reductase inhibitors and bile acid sequestrants for hypercholesterolemia. Cardiology, 1990, 77(Suppl 4):33-38.
17.	Pritzker LB. Do lipid lowering drugs reduce the risk of coronary heart disease? Crit Rev Clin Lab Sci, 1998, 35(6):603-621.
18.	Charlton-Menys V, Betteridge DJ, Colhoun H, et al. Targets of statin therapy:LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study(CARDS). Clin Chem, 2009, 55(3):473-480.
19.	Mizuno Y, Jacob RF, Mason RP. Inflammation and the development of atherosclerosis. J Atheroscler Thromb, 2011, 18(5):351-358.
20.	Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Eng J Med, 1994, 331(7):417-424.
21.	Modena MG, Bonetti L, Coppi F, et al. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol, 2002, 40(3):505-510.
22.	Maack C, Kartes T, Kilter H, et al. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation, 2003, 108(13):1567-1574.
23.	Hindler K, Shaw AD, Samuels J, et al. Improved postoperative outcomes associated with preoperative statin therapy. Anesthesiology, 2006, 105(6):1260-1272.
24.	Huhle G, Abletshauser C, Mayer N, et al. Reduction of platelet activity markers in type II hypercholesterolemic patients by a HMG-CoA-reductase inhibitor. Thromb Res, 1999, 95(5):229-234.
25.	Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med, 1997, 336(20):1429-1434.
26.	Youn YN, Park SY, Hwang Y, et al. Impact of high-dose statin pretreatment in patients with stable angina during off-pump coronary artery bypass. Korean J Thorac Cardiovasc Surg, 2011, 44(3):208-214.
27.	Neher MD, Weckbach S, Flierl MA, et al. Molecular mechanisms of inflammation and tissue injury after major trauma--is complement the "bad guy"? J Biomed Sci, 2011, 18:90.
28.	Boehm J, Hauner K, Grammer J, et al. Tumor necrosis factor-α-863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery. Eur J Cardiothorac Surg, 2011, 40(1):e50-e54.
29.	Lai WT, Lee KT, Chu CS, et al. Influence of withdrawal of statin treatment on proinflammatory response and fibrinolytic activity in humans:an effect independent on cholesterol elevation. Int J Cardiol, 2005, 98(3):459-464.
30.	Bruni F, Pasqui AL, Pastorelli M, et al. Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects. Int J Cardiol, 2004, 95(2-3):269-274.
31.	Alber HF, Frick M, Suessenbacher A, et al. Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study. Am Heart J, 2006, 151(1):139.
32.	Dereli Y, Ege E, Kurban S, et al. Pre-operative atorvastatin therapy to decrease the systemic inflammatory response after coronary artery bypass grafting. J Int Med Res, 2008, 36(6):1248-1254.
33.	Krivoy N, Adler Z, Saloma R, et al. Targeting C-reactive protein levels using high-dose atorvastatin before coronary artery bypass graft surgery. Exp Clin Cardiol, 2008, 13(4):171-174.

1. Kovacević R, Majkić-Singh N, Ignjatović S, et al. Troponin T levels in detection of perioperative myocardial infarction after coronary artery bypass surgery. Clin Lab, 2004, 50(7-8):437-445.
2. Noora J, Ricci C, Hastings D, et al. Determination of troponin I release after CABG surgery. J Card Surg, 2005, 20(2):129-135.
3. Ioannidis JP, Karvouni E, Katritis DG. Mortality risk conferred by small elevations of creatine kinase-MB isoenzyme after percutaneous intervention. J Am Coll Cardiol, 2003, 42(8):1406-1411.
4. Ellis SG, Chew D, Chan A, et al. Death following creatine kinase-MB elevation after coronary intervention:identification of an early risk period:importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy. Circulation, 2002, 106(10):1205-1210.
5. Klatte K, Chaitman BR, Theroux P, et al. Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release:results from the GUARDIAN trial. J Am Coll Cardiol, 2001, 38(4):1070-1077.
6. Steuer J, Hörte LG, Lindahl B, et al. Impact of perioperative myocar-dial injury on early and long-term outcome after coronary artery bypass grafting. Eur Heart J, 2002, 23(15):1219-1227.
7. Herrmann J, Lerman A, Baumgart D, et al. Preprocedural statin medication reduces the extent of periprocedural non-Q-wave myocardial infarction. Circulation, 2002, 106(17):2180-2183.
8. Pasceri V, Patti G, Nusca A, et al. Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention:results from the ARMYDA(Atorvastatin for Reduction of MYocardial Damage during Angioplasty)study. Circulation, 2004, 110(6):674-678.
9. Chan AW, Bhatt DL, Chew DP, et al. Relation of inflammation and benefit of statins after percutaneous coronary intervention.Circulation, 2003, 107(13):1750-1756.
10. Briguori C, Visconti G, Focaccio A, et al. Novel approaches for preventing or limiting events(Naples)II trial:impact of a single high loading dose of atorvastatin on periprocedural myocardial infar-ction. J Am Coll Cardiol, 2009, 54(23):2157-2163.
11. Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes:the MIRACL study:a randomized controlled trial. JAMA, 2001, 285(13):1711-1718.
12. Yun KH, Jeong MH, Oh SK, et al. The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients with acute coronary syndrome. Int J Cardiol, 2009, 137(3):246-251.
13. Christenson JT. Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG. Eur J Cardiothorac Surg, 1999, 15(4):394-400.
14. Thygesen K, Alpert JS, White HD. Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J, 2007, 28(20):2525-2538.
15. Desager JP, Horsmans Y.Clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors.Clin Pharmacokinet, 1996, 31(5):348-371.
16. Erkelens DW. Combination drug therapy with HMG CoA reductase inhibitors and bile acid sequestrants for hypercholesterolemia. Cardiology, 1990, 77(Suppl 4):33-38.
17. Pritzker LB. Do lipid lowering drugs reduce the risk of coronary heart disease? Crit Rev Clin Lab Sci, 1998, 35(6):603-621.
18. Charlton-Menys V, Betteridge DJ, Colhoun H, et al. Targets of statin therapy:LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study(CARDS). Clin Chem, 2009, 55(3):473-480.
19. Mizuno Y, Jacob RF, Mason RP. Inflammation and the development of atherosclerosis. J Atheroscler Thromb, 2011, 18(5):351-358.
20. Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Eng J Med, 1994, 331(7):417-424.
21. Modena MG, Bonetti L, Coppi F, et al. Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol, 2002, 40(3):505-510.
22. Maack C, Kartes T, Kilter H, et al. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation, 2003, 108(13):1567-1574.
23. Hindler K, Shaw AD, Samuels J, et al. Improved postoperative outcomes associated with preoperative statin therapy. Anesthesiology, 2006, 105(6):1260-1272.
24. Huhle G, Abletshauser C, Mayer N, et al. Reduction of platelet activity markers in type II hypercholesterolemic patients by a HMG-CoA-reductase inhibitor. Thromb Res, 1999, 95(5):229-234.
25. Ommen SR, Odell JA, Stanton MS. Atrial arrhythmias after cardiothoracic surgery. N Engl J Med, 1997, 336(20):1429-1434.
26. Youn YN, Park SY, Hwang Y, et al. Impact of high-dose statin pretreatment in patients with stable angina during off-pump coronary artery bypass. Korean J Thorac Cardiovasc Surg, 2011, 44(3):208-214.
27. Neher MD, Weckbach S, Flierl MA, et al. Molecular mechanisms of inflammation and tissue injury after major trauma--is complement the "bad guy"? J Biomed Sci, 2011, 18:90.
28. Boehm J, Hauner K, Grammer J, et al. Tumor necrosis factor-α-863 C/A promoter polymorphism affects the inflammatory response after cardiac surgery. Eur J Cardiothorac Surg, 2011, 40(1):e50-e54.
29. Lai WT, Lee KT, Chu CS, et al. Influence of withdrawal of statin treatment on proinflammatory response and fibrinolytic activity in humans:an effect independent on cholesterol elevation. Int J Cardiol, 2005, 98(3):459-464.
30. Bruni F, Pasqui AL, Pastorelli M, et al. Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects. Int J Cardiol, 2004, 95(2-3):269-274.
31. Alber HF, Frick M, Suessenbacher A, et al. Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study. Am Heart J, 2006, 151(1):139.
32. Dereli Y, Ege E, Kurban S, et al. Pre-operative atorvastatin therapy to decrease the systemic inflammatory response after coronary artery bypass grafting. J Int Med Res, 2008, 36(6):1248-1254.
33. Krivoy N, Adler Z, Saloma R, et al. Targeting C-reactive protein levels using high-dose atorvastatin before coronary artery bypass graft surgery. Exp Clin Cardiol, 2008, 13(4):171-174.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Single High-dose Atorvastatin Loading before Off-pump Coronary Artery Bypass Grafting Alleviates Postoperative Myocardial Injury: A Prospective Randomized Controlled Trial

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