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Prof. Nawwar Al-Attar
Use of aspirin following coronary bypass surgery improves both graft patency - particularly in venous grafts - and operative outcome. Surgeons have been reluctant to employ early antiplatelet therapy for patients undergoing CABG because of the risk of increased bleeding, but several studies have consistently shown the benefit of initiating or continuing aspirin therapy.
Antiplatelet therapy has an established role in primary and secondary prevention of atherothrombotic disease. Long term aspirin therapy in patients with coronary artery disease (CAD) has recognised efficacy in reducing the risk of death, myocardial infarction, and stroke (1) as well as preventing ischemic complications (2). Graft stenosis and occlusion after CABG are due to a number of factors related to the quality of surgical anastomosis, the state of the graft, its type and the patient’s coagulation status in the perioperative period. Altogether these factors may contribute to the formation of a thrombus at the anastomotic site. The role of antiplatelet therapy in graft patency becomes substantial as it will reduce the formation of thrombus, prevent graft occlusion, and protect graft patency (3,4,5).
Clinically, venous grafts - mainly the saphenous vein- , are primarily involved since they are widely used and have an occlusion rate of 8-18% due to thrombus formation within the first postoperative month after CABG (6,7). Later venous graft occlusion is due to intimal hyperplasia, with a total occlusion rate of 15-30% in the first year (8) and a combination of intimal hyperplasia plus progressive atherosclerotic obstruction thereafter.
Antiplatelet drugs, and particularly aspirin, has been shown to have a beneficial effect on vein graft patency during the first year after CABG when administered in the early postoperative period – when vein graft attrition is mainly caused by thrombotic occlusion. (2,3). The beneficial effects of aspirin on vein graft patency are attenuated after the first year since later phases of intimal hyperplasia and vein graft artherosclerosis are not influenced by aspirin therapy. On the other hand, long-term survival and outcome after CABG is significantly related to venous graft patency and aspirin improved vein graft patency early after surgery and at 1 year after surgery, with vein grafts placed to smaller vessels gaining the major benefit. However no similar benefit was conferred when only internal mammary artery (IMA) grafting was used for CABG.
Debate regarding what the optimal dose must consider the effects of cardiopulmonary bypass or surgical trauma on platelet function - off-pump CABG (OPCAB) being associated with a lesser degree of platelet function alteration. In on-pump CABG, low dose aspirin has sufficient biochemical activity to inhibit platelet thromboxane production in patients with atherosclerosis (11). However, early postoperative platelet aggregation is not inhibited by low dose aspirin (100 mg) after coronary bypass surgery (12). The antiplatelet trialists’ collaboration showed a pooled odds reduction for graft occlusion of 44% in five trials comparing low-dose aspirin (<325 mg/day), and of 50% in nine trials comparing high-dose aspirin (>500 mg/day) with placebo or control group. There was no statistical difference in occlusion rates between low-dose and high-dose aspirin(1). Lim et al showed that medium dose aspirin (325 mg) may more successfully reduce graft occlusion than do low dose (100 mg) regimes within the first year after coronary surgery (13).
Preoperative discontinuation of aspirin therapy in patients under continuous antiplatelet treatment before CABG was associated with an increased risk of death (OR 1.79) but this risk was reduced when aspirin was used within 48hrs after surgery. The use of aspirin in the postoperative period was not associated with increased adverse events (14). This was confirmed by a meta-analysis that showed that aspirin discontinuation had a detrimental impact on the risk of adverse events with an OR =2.20 (15,16). Patients with previous PCI and stents had a significantly higher risk of adverse events (OR 89.78) following cessation of antiplatelet treatment. In the case of noncardiac surgery, aspirin administration did not increase the severity of bleeding complications nor did it influence the perioperative mortality from bleeding complications. The general consensus is that withdrawal of aspirin treatment has ominous prognostic implication in patients with coronary heart disease, especially in those with intracoronary stents and should be advocated only when the bleeding risk clearly outweighs that of atherothrombotic events (17).
Thromboembolic events can be observed in spite of continuous antiplatelet therapy. This has been coined “nonresponse’ or ‘aspirin resistance’. It has been described affecting more than two thirds of the patients early after CABG (18).
A comparative study of graft patency with clopidogrel plus aspirin versus clopidogrel in the early postoperative phase after CABG showed no significant differences between the two groups. Nevertheless, there was an observed trend toward higher patency rates in patients treated with clopidogrel plus aspirin than those in the clopidogrel group (19).
1) Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trials of antiplatelet therapy. II: Maintenance of vascular graft or arterial patency by antiplatelet therapy. Br Med J 1994;308:159–68. 2) Mangano DT, for the Multicenter Study of Perioperative Ischemia Research Group. Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002;347:1309-17. 3) Goldman S, Copeland J, Moritz T, Henderson W, Zadina K, Ovitt T, Doherty J, Read R, Chesler E, Sako Y. Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration Cooperative Study. Circulation 1988;77:1324-32. 4) Stein PD, Schunemann HJ, Dalen JE, et al. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126(suppl 3):600S– 8S. 5) Poston RS, Gu J, Brown JM, et al. Endothelial injury and acquired aspirin resistance as promoters of regional thrombin formation and early vein graft failure after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2006;131:122–30. 6) Fuster V, Chesebro JH. Aorto-coronary artery vein graft disease: experimental and clinical approach for the understanding of the role of platelets and platelet inhibitors. Circulation 1985;72(Suppl. V):65—70. 7) Fuster V, Chesebro JH. Role of platelets and platelet inhibitors in aortocoronary artery vein-graft disease. Circulation 1986;73:227-32. 8) Cooper GJ, Underwood MJ, Deverall PB. Arterial and venous conduits for coronary artery bypass. A current review. Eur J Cardiothorac Surg 1996;10:129-40. 9) Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am Coll Cardiol 1996;28:616—26. 10) Stein PD, Schünemann HJ, Dalen JE, Guttermann D. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts. Chest 2004;126:600S—8S. 11) Weksler BB, Pett SB, Alonso D, Richter RC, Stelzer P, Subramanian V, et al. Differential inhibition by aspirin of vascular and platelet prostaglandin synthesis in atherosclerotic patients. N Engl J Med 1983;308:800-5. 12) Zimmermann N, Kienzle P, Weber AA, Winter J, Gams E, Schror K, et al. Aspirin resistance after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2001;121:982-4. 13) Lim E, Ali Z, Ali A, Routledge T, Edmonds L, Altman DG, Large S. Indirect comparison meta-analysis of aspirin therapy after coronary surgery. BMJ. 2003;327:1309. Erratum in: BMJ. 2004 Jan 17;328(7432):147. 14) Angano DT, Multicenter Study of Perioperative Ischemia Research Group. Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002;347:1309-17. 15) 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. Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients. Ann Thorac Surg 2000;70:1986—90 16) Biondi-Zoccai GG, Lotrionte M, Agostoni P, Abbate A, Fusaro M, Burzotta F, Testa L, Sheiban I, Sangiorgi G. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J 2006;27:2667-74. 17) Zimmermann N, Gams E, Hohlfeld T. Aspirin in coronary artery bypass surgery: new aspects of and alternatives for an old antithrombotic agent. Eur J Cardiothorac Surg. 2008 Jul;34(1):93-108. 18) Zimmermann N, Wenk A, Kim U, Kienzle P, Weber AA, Gams E, Schro¨r K, Hohlfeld T. Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery. Circulation 2003;108:542—7. 19) Changqing Gao, Chonglei Ren, Dong Li and Libing Li Clopidogrel and Aspirin Versus Clopidogrel Alone on Graft Patency After Coronary Artery Bypass Grafting Ann Thorac Surg 2009;88:59-62