Lipid-lowering therapy and coronary artery bypass graft surgery: What are the benefits?

Current Opinion in Cardiology

Volumn 26, Issue 6, 2011, Pages 508-517

  Kulik, Alexander ^a   Ruel, Marc ^b  

^a FLORIDA ATLANTIC UNIVERSITY   (United States)

^b UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

Author keywords

coronary artery bypass graft surgery; coronary artery disease; lipid lowering therapy; saphenous vein graft disease; statins

Indexed keywords

AMIODARONE; ATORVASTATIN; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; COLESTIPOL; CREATINE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN; MEVINOLIN; MYOGLOBIN; NICOTINIC ACID; NITRIC OXIDE; PLACEBO; ROSUVASTATIN; SIMVASTATIN; TROPONIN I;

ATHEROSCLEROSIS; CORONARY ARTERY BYPASS GRAFT; DISEASE COURSE; DRUG DOSE COMPARISON; DRUG MEGADOSE; ENDOTHELIAL PROGENITOR CELL; GRAFT OCCLUSION; GRAFT PATENCY; HEART ATRIUM FIBRILLATION; HEART MUSCLE INJURY; HUMAN; INFLAMMATION; MEDLINE; MORTALITY; PERIOPERATIVE PERIOD; POSTOPERATIVE CARE; PRIORITY JOURNAL; REVIEW; STROKE; SURGICAL RISK; TREATMENT DURATION; TREATMENT OUTCOME; VEIN GRAFT DISEASE;

ANTICHOLESTEREMIC AGENTS; CORONARY ARTERY BYPASS; CORONARY ARTERY DISEASE; DISEASE PROGRESSION; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; KIDNEY DISEASES; MYOCARDIUM; PERIOPERATIVE CARE; PREOPERATIVE CARE; STROKE; TIME FACTORS; TREATMENT OUTCOME;

EID: 80054683528     PISSN: 02684705     EISSN: 15317080     Source Type: Journal    
DOI: 10.1097/HCO.0b013e32834b9fb1     Document Type: Review

References (70)

1. Grundy SM. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med 1988;319:24-33.
2. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterollowering treatment: prospective meta-analysis of data from 90056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-1278.
3. Rossouw JE. Lipid-lowering interventions in angiographic trials. Am J Cardiol 1995;76:86C-92C.
4. Calabro P, Yeh ET. The pleiotropic effects of statins. Curr Opin Cardiol 2005;20:541-546. (Pubitemid 41565340)
5. Armitage J. The safety of statins in clinical practice. Lancet 2007;370:1781-1790. (Pubitemid 350137473)
6. Kulik A, Ruel M. Statins and coronary artery bypass graft surgery: preoperative and postoperative efficacy and safety. Expert Opin Drug Saf 2009;8:559-571.
7. Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998;97:916-931. (Pubitemid 28113931)
8. Daida H, Yokoi H, Miyano H, et al. Relation of saphenous vein graft obstruction to serum cholesterol levels. J Am Coll Cardiol 1995;25:193-197.
9. Indolfi C, Cioppa A, Stabile E, et al. Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury. J Am Coll Cardiol 2000;35:214-221. (Pubitemid 30061283)
10. Porter KE, Naik J, Turner NA, et al. Simvastatin inhibits human saphenous vein neointima formation via inhibition of smooth muscle cell proliferation and migration. J Vasc Surg 2002;36:150-157. (Pubitemid 41122904)
11. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. The Post Coronary Artery Bypass Graft Trial Investigators. N Engl J Med 1997;336:153-162.
12. Knatterud GL, Rosenberg Y, Campeau L, et al. Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary artery bypass graft trial. Post CABG Investigators. Circulation 2000;102:157-165. (Pubitemid 30451771)
13. Kulik A, Brookhart MA, Levin R, et al. Impact of statin use on outcomes after coronary artery bypass graft surgery. Circulation 2008;118:1785-1792.
14. Kulik A, Levin R, Ruel M, et al. Patterns and predictors of statin use after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg 2007;134:932-938. (Pubitemid 47445596)
15. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961-972.
16. Kulik A, Shrank WH, Levin R, Choudhry NK. Adherence to statin therapy in elderly patients after hospitalization for coronary revascularization. Am J Cardiol 2011;107:1409-1414. In this observational study, the authors reported lower adherence to statin therapy amongst MI patients treated with percutaneous or surgical revascularization compared with patients treated with medical therapy.
17. Cannon CP, Steinberg BA, Murphy SA, et al. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol 2006;48:438-445. (Pubitemid 44109954)
18. Chello M, Patti G, Candura D, et al. Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery. Crit Care Med 2006;34:660-667.
19. Chello M, Anselmi A, Spadaccio C, et al. Simvastatin increases neutrophil apoptosis and reduces inflammatory reaction after coronary surgery. Ann Thorac Surg 2007;83:1374-1380. (Pubitemid 46440750)
20. Nakamura K, Masuda H, Kariyazono H, et al. Effects of atorvastatin and aspirin combined therapy on inflammatory responses in patients undergoing coronary artery bypass grafting. Cytokine 2006;36:201-210. (Pubitemid 46529472)
21. Dereli Y, Ege E, Kurban S, et al. Preoperative atorvastatin therapy to decrease the systemic inflammatory response after coronary artery bypass grafting. J Int Med Res 2008;36:1248-1254.
22. Sasmazel A, Baysal A, Fedekar A, et al. The effect of statin therapy on stimulation of endothelium-derived nitric oxide before and after coronary artery bypass surgery. Heart Surg Forum 2010;13:E243-E246. In this trial, atorvastatin treatment before CABG was noted to increase perioperative nitric oxide production.
23. Spadaccio C, Pollari F, Casacalenda A, et al. Atorvastatin increases the number of endothelial progenitor cells after cardiac surgery: a randomized control study. J Cardiovasc Pharmacol 2010;55:30-38. In another important contibution from this active research group, the authors documented higher amounts of EPCs before and after CABG in patients randomized to treatment with atorvastatin compared with placebo.
24. Pliquett RU, Cornish KG, Peuler JD, Zucker IH. Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation 2003;107:2493-2498. (Pubitemid 36605234)
25. Korantzopoulos P, Kountouris E, Kolettis T, Siogas K. Anti-inflammatory and antioxidant actions of statins may favorably affect atrial remodeling in atrial fibrillation. Am J Cardiol 2004;93:1200. (Pubitemid 38521064)
26. Pound EM, Kang JX, Leaf A. Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes. J Lipid Res 2001;42:346-351. (Pubitemid 32270057)
27. Patti G, Chello M, Candura D, et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Circulation 2006;114:1455-1461. (Pubitemid 44526999)
28. Kourliouros A, De Souza A, Roberts N, et al. Dose-related effect of statins on atrial fibrillation after cardiac surgery. Ann Thorac Surg 2008;85:1515-1520. (Pubitemid 351618357)
29. Song YB, On YK, Kim JH, et al. The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery. Am Heart J 2008;156:373e316-373e379.
30. Lertsburapa K, White CM, Kluger J, et al. Preoperative statins for the prevention of atrial fibrillation after cardiothoracic surgery. J Thorac Cardiovasc Surg 2008;135:405-411. (Pubitemid 351192943)
31. Mithani S, Akbar MS, Johnson DJ, et al. Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers. J Cardiothorac Surg 2009;4:61.
32. Kulik A, Singh JP, Levin R, et al. Association between statin use and the incidence of atrial fibrillation following hospitalization for coronary artery disease. Am J Cardiol 2010;105:1655-1660. In an observational study of over 29 000 patients, this article demonstrated that statin therapy after hospitalization for coronary artery disease was associated with a significantly lower incidence of atrial fibrillation during long-term follow-up.
33. Liakopoulos OJ, Choi YH, Kuhn EW, et al. Statins for prevention of atrial fibrillation after cardiac surgery: a systematic literature review. J Thorac Cardiovasc Surg 2009;138:678-686; e671.
34. Winchester DE, Wen X, Xie L, Bavry AA. Evidence of preprocedural statin therapy a meta-analysis of randomized trials. J Am Coll Cardiol 2010;56:1099-1109. This recently performed meta-analysis demonstrated a significant association between preoperative statin therapy and a lower risk of postoperative atrial fibrillation.
35. Chen WT, Krishnan GM, Sood N, et al. Effect of statins on atrial fibrillation after cardiac surgery: a duration and dose-response meta-analysis. J Thorac Cardiovasc Surg 2010;140:364-372. In their meta-analysis of eight trials, these authors found a significant relationship between preoperative statin therapy and a lower risk of postoperative atrial fibrillation. No dose response was seen, however, as the authors found no association between higher statin doses and a lower risk of atrial fibrillation.
36. Kourliouros A, Valencia O, Hosseini MT, et al. Preoperative high-dose atorvastatin for prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. J Thorac Cardiovasc Surg 2011;141:244-248. These authors evaluated the impact of high-dose atorvastatin therapy on the prevention of atrial fibrillation after cardiac surgery in a randomized controlled trial of 104 patients. High-dose atorvastatin did not significantly reduce postoperative atrial fibrillation, as compared with the use of low-dose atorvastatin.
37. Liakopoulos OJ, Choi YH, Haldenwang PL, et al. Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30 000 patients. Eur Heart J 2008;29:1548-1559. (Pubitemid 351881985)
38. Huffmyer JL, Mauermann WJ, Thiele RH, et al. Preoperative statin administration is associated with lower mortality and decreased need for postoperative hemodialysis in patients undergoing coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2009;23:468-473.
39. Billings FT 4th, Pretorius M, Siew ED, et al. Early postoperative statin therapy is associated with a lower incidence of acute kidney injury after cardiac surgery. J Cardiothorac Vasc Anesth 2010;24:913-920. These authors noted that early postoperative statin therapy was associated with a lower risk of acute kidney injury in this observational study of cardiac surgery patients. Conversely, statin withdrawal was associated with a higher risk of kidney injury.
40. Mithani S, Kuskowski M, Slinin Y, et al. Dose-dependent effect of statins on the incidence of acute kidney injury after cardiac surgery. Ann Thorac Surg 2011;91:520-525. In a study of over 2000 cardiac surgery patients, these authors found no significant association between statin therapy and the risk of acute kidney injury after cardiac surgery.
41. Christenson JT. Preoperative lipid-control with simvastatin reduces the risk of postoperative thrombocytosis and thrombotic complications following CABG. Eur J Cardiothorac Surg 1999;15:394-399; discussion 399-400.
42. Christenson JT. Preoperative lipid control with simvastatin protects coronary artery bypass grafts from obstructive graft disease. Am J Cardiol 2001;88:896-899; A898. (Pubitemid 32995928)
43. Mannacio VA, Iorio D, De Amicis V, et al. Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery: a randomized trial. J Thorac Cardiovasc Surg 2008;136:1541-1548.
44. Ege E, Dereli Y, Kurban S, Sarigul A. Atorvastatin pretreatment diminishes the levels of myocardial ischemia markers early after CABG operation: an observational study. J Cardiothorac Surg 2010;5:60. In a small observational study, these authors reported that preoperative treatment with atorvastatin was associated with lower marker levels of myocardial injury after coronary artery bypass.
45. Aboyans V, Labrousse L, Lacroix P, et al. Predictive factors of stroke in patients undergoing coronary bypass grafting: statins are protective. Eur J Cardiothorac Surg 2006;30:300-304. (Pubitemid 44056338)
46. Koenig MA, Grega MA, Bailey MM, et al. Statin use and neurologic morbidity after coronary artery bypass grafting: a cohort study. Neurology 2009;73:2099-2106.
47. Bouchard D, Carrier M, Demers P, et al. Statin in combination with beta-blocker therapy reduces postoperative stroke after coronary artery bypass graft surgery. Ann Thorac Surg 2011;91:654-659. In this interesting observational study, the authors found that the combination of statin therapy and p-blocker therapy together led to a significant reduction in the risk of stroke after coronary bypass surgery.
48. Pan W, Pintar T, Anton J, et al. Statins are associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery. Circulation 2004;110(11 Suppl 1):II45-II49. (Pubitemid 39263697)
49. Collard CD, Body SC, Shernan SK, et al. Preoperative statin therapy is associated with reduced cardiac mortality after coronary artery bypass graft surgery. J Thorac Cardiovasc Surg 2006;132:392-400. (Pubitemid 44092868)
50. Vaduganathan M, Stone NJ, Lee R, et al. Perioperative statin therapy reduces mortality in normolipidemic patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 2010;140:1018-1027. Studying the outcomes of over 3000 cardiac surgery patients, these authors found that perioperative statin therapy was associated with a lower risk of mid-term mortality after surgery, even among patients with normal baseline lipid levels, suggesting that the beneficial effects of statins may extend beyond their lipidlowering ability.
51. Takagi H, Umemoto T. A meta-analysis of controlled studies of preoperative statin therapy for prevention of postoperative mortality in cardiac surgery. J Thorac Cardiovasc Surg 2009;138:790-791; author reply 792.
52. Cashin-Hemphill L, Mack WJ, Pogoda JM, et al. Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up. JAMA 1990;264:3013-3017.
53. Aihara K, Miyauchi K, Kasai T, et al. Long-term efficacy of pravastatin therapy in diabetic patients undergoing complete coronary revascularization. J Atheroscler Thromb 2010;17:350-355. These authors found a significant association between pravastatin therapy and a lower risk of long-term mortality following coronary bypass in this observational study.
54. Gan HL, Zhang JQ, Bo P, et al. Statins decrease adverse outcomes in coronary artery bypass for extensive coronary artery disease as well as left main coronary stenosis. Cardiovasc Ther 2010;28:70-79. Performing propensity-matched analysis, the authors noted a significantly lower risk of long-term mortality after coronary artery bypass surgery in patients treated with statins compared with those not treated with statins.
55. Carrier M, Cossette M, Pellerin M, et al. Statin treatment equalizes long-term survival between patients with single and bilateral internal thoracic artery grafts. Ann Thorac Surg 2009;88:789-795; discussion 795. In this interesting observational study, these authors found the survival benefit associated with statin treatment after coronary surgery was similar in magnitude to the benefit associated with two internal thoracic artery grafts compared with the use of one.
56. Borger MA, Seeburger J, Walther T, et al. Effect of preoperative statin therapy on patients undergoing isolated and combined valvular heart surgery. Ann Thorac Surg 2010;89:773-779; discussion 779-780. These authors performed an observational study of over 10 000 patients to evaluate whether the benefits of statins extend to those recovering from valve surgery. Whereas no survival benefit was seen amongst the entire cohort, statin therapy was associated with a significant improvement in survival for patients who underwent concomitant coronary bypass at the time of the valve operation.
57. Eagle KA, Guyton RA, Davidoff R, et al. 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 2004;110:e340-e437.
58. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435. (Pubitemid 40471450)
59. Shah SJ, Waters DD, Barter P, et al. Intensive lipid-lowering with atorvastatin for secondary prevention in patients after coronary artery bypass surgery. J Am Coll Cardiol 2008;51:1938-1943. (Pubitemid 351636440)
60. Brilakis ES, de Lemos JA, Cannon CP, et al. Outcomes of patients with acute coronary syndrome and previous coronary artery bypass grafting [from the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT-TIMI 22) and the AggrastattoZocor (A to Z) trials]. Am J Cardiol 2008;102:552-558.
61. Ouattara A, Benhaoua H, Le Manach Y, et al. Perioperative statin therapy is associated with a significant and dose-dependent reduction of adverse cardiovascular outcomes after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2009;23:633-638. In this observational study, the authors noted a significant reduction in the incidence of perioperative cardiac events in patients who received high-dose statin therapy before coronary surgery compared with those treated with low-dose statins.
62. Hata M, Takayama T, Sezai A, et al. Efficacy of aggressive lipid controlling therapy for preventing saphenous vein graft disease. Ann Thorac Surg 2009;88:1440-1444. Using angioscopy 1 year after surgery, these authors found a lower incidence of yellow plaque and thrombus in the vein grafts of patients who had LDL levels less than 80mg/dl compared with patients who had LDL levels more than 100mg/dl, suggesting that aggressive lipid-lowering therapy may prevent the development of saphenous vein graft disease.
63. Kulik A, Voisine P, Mathieu P, et al. Statin therapy and saphenous vein graft disease after coronary bypass surgery: analysis from the CASCADE randomized trial. Ann Thorac Surg 2011 (in press). In this post-hoc analysis of a randomized controlled trial, these authors reported a significantly higher graft patency among patients with LDL levels less than 100 mg/dl 1 year after surgery compared with patients with LDL levels more than 100mg/dl. However, further LDL reduction to less than 70 mg/dl did not lead to any further improvement in graft patency.
64. Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA 2007;297:177-186. (Pubitemid 46089734)
65. Ho PM, Magid DJ, Shetterly SM, et al. Medication nonadherence is associated with a broad range of adverse outcomes in patients with coronary artery disease. Am Heart J 2008;155:772-779. (Pubitemid 351410514)
66. Williams JB, Delong ER, Peterson ED, et al. Secondary prevention after coronary artery bypass graft surgery: findings of a national randomized controlled trial and sustained society-led incorporation into practice. Circulation 2011;123:39-45. In a recent multicenter randomized controlled trial, the Society of Thoracic Surgeons demonstrated that continuous quality improvement efforts could lead to an increase in the administration of lipid-lowering therapy after coronary surgery.
67. Conway AM, Musleh G. Which is the best statin forthe postoperative coronary artery bypass graft patient? Eur J Cardiothorac Surg 2009;36:628-632.
68. Sedjo RL, Cox ER. Lowering copayments: impact of simvastatin patent expiration on patient adherence. Am J Manag Care 2008;14:813-818.
69. Frick MH, Syvanne M, Nieminen MS, et al. Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group. Circulation 1997;96:2137-2143.
70. Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009;361:2113-2122. This recent randomized trial demonstrated the effectiveness of extended-release niacin, when combined with a statin, in the reduction of carotid intima-media thickness, as compared with the addition of ezetimibe.