PRO: Aspirin should be continued perioperatively for cardiac surgery
Mary Fillinger, MD
Associate Professor of Anesthesiology
Dartmouth Medical School
Maintenance of graft patency is crucial to the success of coronary artery bypass graft (CABG) surgery. Multiple factors affect early and long-term graft patency.1-5 Platelet activation and aggregation resulting in thrombotic occlusion within bypass grafts plays a major role in early graft closure.6 Activated platelets also play a dominant role in inflammation.7 Not only do activated platelets produce and secrete key inflammatory modulators, but they immediately and directly trigger an inflammatory response of the endothethial cell wall by shedding CD40 ligand.8 Neointimal hyperplasia occurring in venous grafts acts as a foundation for late graft failure from atherosclerotic obstruction.6
Although plaque rupture with subsequent thrombus formation is the proximate cause of myocardial infarction (MI), inflammation plays a key role in the initiation and progression of atherosclerotic coronary artery disease (CAD).9 The benefits of aspirin in patients with CAD appear to be related primarily to its antiplatelet and anti-inflammatory effects, although other cellular effects of aspirin, such as antioxidant effects, may play a role.7,10,11 The antithrombotic effect of aspirin is mediated primarily by the irreversible acetylation and inactivation of platelet enzyme cyclooxygenase (COX) for the 7- to 10-day lifespan of the platelet. This results in decreased production and release of thromboxane A2, a potent platelet activator and aggregator as well as a potent vasoconstrictor. Insufficient inhibition of platelet function, or aspirin resistance has been reported in up to 30% of persons with CAD12 and after CABG.13 Attenuation of inflammation also appears to play a role in aspirin cardioprotection. Reduction in risk of first MI by aspirin use has been demonstrated to be directly related to patient levels of the inflammatory mediator, C-reactive protein.11
Aspirin is beneficial in patients with CAD. The Antithrombotic Trialists' Collaboration reported that allocation to aspirin therapy resulted in a reduction of the combined outcome of any serious vascular event (non-fatal MI, non-fatal stroke, or vascular death) by about 25%.14 The authors reported a 34% proportional reduction in non-fatal MI, a 25% reduction in non-fatal stroke, and a highly significant 15% reduction in vascular deaths. This reduction in risk was observed not only in patients with acute MI, unstable angina, stroke or transient ischemic attacks, but also among patients with coronary or peripheral arterial disease and those at high risk for embolism. Daily low dose aspirin 75 mg - 150 mg appeared to be as effective as higher doses for long term primary and secondary prevention of occlusive vascular events in all patients at intermediate or high risk for such events.
Perioperative aspirin use has been associated with improved outcomes after cardiac surgery. Aspirin use, whether given one day before operation or within 24 hours thereafter, reduces the frequency of early and long-term saphenous vein graft occlusion when compared with placebo.1-2 Although higher doses were equally effective in maintaining graft patency, aspirin 75 mg to 325 mg per day may be the preferred dosage to reduce harmful side effects. One early randomized controlled trial reported on the effects of preoperative aspirin, 325 mg per day, started the day before CABG compared with aspirin begun six hours after surgery.4 There was no difference between the two groups in terms of early vein graft patency within 7-10 postoperative days. Bleeding complications were found to be higher in the early aspirin group.
Perioperative aspirin use is associated with improved survival after CABG.15,16 The Northern New England Cardiovascular Disease Study Group studied 8,641 consecutive patients undergoing CABG between 1987 and 1991.15 The effect of preoperative aspirin use (within seven days before operation) on mortality was evaluated. Using multivariate analysis, patients using preoperative aspirin had a 45% reduction in in-hospital mortality compared to nonusers (odds ratio [OR] = 0.55, 95% confidence interval [0.31, 0.98]). Preoperative aspirin use was not associated with a significant increase in bleeding, blood product requirements or reexploration for bleeding compared to non aspirin users.
Mangano reported on the outcomes of 5,065 patients undergoing CABG at 70 centers in 17 countries between 1996 and 2000.16 The relation between early aspirin use, defined as aspirin ingestion within 48 hours after revascularization, and fatal and nonfatal outcomes was evaluated on the 5,022 patients who survived the first 48 hours after surgery. Early aspirin use after CABG, when compared with non aspirin use, was associated with a 68% reduction in overall mortality, a 48% reduction in the incidence of non-fatal MI, a 50% reduction in the incidence of stroke, a 74% reduction in renal failure, and a 62% reduction in the incidence of bowel infarction. Aspirin use was not associated with an increased risk of bleeding complications. Discontinuation of aspirin use before surgery was associated with an increase risk for death (OR 1.79, [1.18, 2.69], p=0.01).
Harmful effects of perioperative aspirin therapy in cardiac surgery include increased postoperative mediastinal blood loss, increased reexploration for bleeding, and increased blood transfusions with attendant risk of infection and other transfusion-related problems.4,5,17-20 Other and more recent studies indicate that preoperative ASA use is not an important predictor of bleeding complications,15,21-25 even after repeat CABG26 and despite an increase in preoperative aspirin and heparin use up until the time of surgery.27 The reduction in bleeding complications may be related to newer and current practice patterns of autotransfusion of shed mediastinal blood, strict transfusion criteria, and the use of antifibrinolytic agents for bleeding prophylaxis, that were not reflected in the earlier trials.28-31
The American College of Chest Physicians (ACCP) presented their 2004 evidence-based guidelines for antithrombotic therapy in patients undergoing CABG.1 Although continuation of preoperative aspirin is associated with a survival benefit after CABG without an increase in bleeding complications,15,16 the ACCP recommends aspirin, 75 to 325 mg/day, starting 6 hours after operation over preoperative aspirin to avoid bleeding complications.
In summary, aspirin should be continued perioperatively for cardiac surgery because of its positive effects on graft patency and survival. Current blood conservation practice patterns may mitigate aspirin's adverse side-effects. Questions regarding optimum aspirin dosage and timing of administration, benefits of additional antiplatelet agent administration, and the role of nitric-oxide donating aspirin to reduce graft spasm and neointima formation32 are still to be elucidated.
- Stein PD, Schnemann HJ, Dalen JE, Gutterman D: Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126:600S-608S
- Goldman S, Zadina K, Mortiz T, et al: Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery. J Am Coll Cardiol 2004; 44:2149-56
- Goldman S, Copeland J, Moritz T, et al: Long term graft patency (3 years) after coronary artery surgery: effects of aspirin. Results of a VA cooperative study. Circulation 1994; 89:1138-43
- Goldman S, Copeland J, Moritz T, et al: Starting aspirin therapy after operation. Effects on early graft patency. Circulation 1991; 84:520-6
- Goldman W, Copeland J, Mortiz T, et al: Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration Cooperative Study. Circulation 1988; 6:1324-32
- Motwani JG, Topol EJ: Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998; 97:916-31
- Topol EJ: Aspirin with bypass surgery - from taboo to new standard of care. N Engl J Med 2002; 17:1359-60
- Henn V, Slupsky JR, Gr„fe, et al: CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391:591-4
- Hansson GK: Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352:1685-95
- Awtry EH, Loscalzo J: Cardiovascular drugs. Aspirin. Circulation 2000; 101:1206-18
- Ridker PM, Cushman M, Stampfer MJ, et al: Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 14:973-9
- Lange RA, Hillis, LD: Concurrent antiplatelet and fibrinolytic therapy. N Engl J Med 2005; 12:1248-50
- Zimmerman N, Kienzle P, Weber A, et al: Aspirin resistance after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2001; 121:982-4
- Antithrombotic Trialists' Collaboration: Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71-86
- Dacey LJ, Munoz JJ, Johnson ER, et al: Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients. Ann Thorac Surg 2000; 70:1986-90
- Mangano DT: Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002; 17:1309-17
- Ferraris VA, Ferraris SP, Moliterno DJ, et al: The Society of Thoracic Surgeons Practice Guideline Series. Aspirin and other anti-platelet agents during operative coronary revascularization. The Society of Thoracic Surgeons, 2003
- Sethi GK, Copeland JG, Goldman S, et al: Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grafting. Department of Veterans Affairs Cooperative Study on Antiplatelet Therapy. J Am Coll Cardiol 1990; 15:15-20
- Kallis P, Tooze JA, Talbot S, et al: Pre-operative aspirin decreases platelet aggregation and increases post-operative blood loss - a prospective, randomized, placebo-controlled, double-blind clinical trial in 100 patients with chronic stable angina. Euro J Cardio Thorac Surg 1994; 8:404-9
- Ferraris VA, Ferraris SP, Joseph O, et al: Aspirin and postoperative bleeding after coronary artery bypass grafting. Ann Surg 2002; 6:820-7
- Rawitscher RE, Jones JW, McCoy TA, et al: A prospective study of aspirin's effect on red blood cell loss in cardiac surgery. J Cardiovasc Surg 1991; 32:1-7
- Reich DL, Patel GC, Vela-Cantos F, et al: Aspirin does not increase homologous blood requirements in elective coronary bypass surgery. Anesth Analg 1994; 79:4-8
- Karwanda SV, Weksler, BB, Gay WA, Subramanian VA. Effect of preoperative antiplatelet drugs on vascular prostacyclin synthesis. Ann Thorac Surg 1987; 43:318-22
- Levy JH: Aspirin and bleeding after coronary artery bypass grafting. Anesth Analg 1994; 79:1-3
- Ferraris VA, Gildengorin V: Predictors of excessive blood use after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1989; 98:492-7
- Tuman KJ, McCarthy RJ, O'Connor CJ, et al: Aspirin does not increase allogeneic blood transfusion in reoperative coronary artery surgery. Anesth Analg 1996; 83:1178-84
- Munoz JJ, Birkmeyer NJO, Dacey LJ, et al: Trends in rates of reexploration for hemorrhage after coronary artery bypass surgery. Ann Thorac Surg 1999; 68:1321-5
- Bjessmo S, Ivert T: Blood loss after coronary artery bypass surgery: relations to patient variables and antithrombotic treatment. Scand Cardiovasc J 2000; 34:438-45
- Sch”nberger JPAM, Bred‚e JJ, van Oeveren W, et al: Preoperative therapy of low-dose aspirin in internal mammary artery bypass operations with and without low-dose aprotinin. J Thorac Cardiovasc Surg 1993; 106:262-7
- Alvarez JM, Jackson LR, Chatwin C, Smolich JJ: Low-dose postoperative aprotinin reduces mediastinal drainage and blood product use in patients undergoing primary coronary artery bypass grafting who are taking aspirin: a prospective, randomized, double-blind, placebo-controlled trial. J Thorac Cardiovasc Surg 2001; 122:457-63
- Pleym H, Stenseth R, Wahba A, et al: Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery. Anesth Analg 2003; 96: 923-8
- Shukla N, Angelini GD, Ascione R, et al: Nitric oxide donating aspirins: novel drugs for the treatment of saphenous vein graft failure. Ann Thorac Surg 2003; 75:1437-42