CON: Aspirin should be continued perioperatively for cardiac surgery
M J Desmond, MRCP, FRCA
The Cardiothoracic Centre Liverpool (UK)
In coronary artery bypass grafting (CABG) the logic of treatment is to revascularize (or improve the vascularity) of the myocardium to relieve symptoms of angina where this is refractory to medical treatment. Depending on the extent and configuration of disease, the intention may also be to improve survival. The risks associated with the procedure are significant and include risks inherent in bypass itself (systemic inflammatory response, embolism), risks associated with ischaemia to vital organs (heart, brain, kidneys and gut), the risks of inadequate myocardial protection and or inadequate revascularisation and the risks of excessive bleeding. It is a rare event for a CABG patient to die directly from the effects of bleeding, but the clinical effects of a prolonged low output state from tamponade or the hemodynamic instability in CABG patients awaiting resternotomy for bleeding will be familiar to anyone working in the specialty. Such circumstances can and do give rise to dysfunction in all the major organ systems, and make their contribution to the overall morbidity and mortality associated with the CABG procedure. The scale of this contribution is hard to quantify from the literature but few would disagree that it is best to avoid excessive bleeding. The importance here of good surgical hemostasis is self evident, nevertheless the proportion of patients undergoing resternotomy for bleeding is approximately 5%,1 and no surgical cause of bleeding is found in as many as one third of such patients. What cannot be answered from the literature is in what proportion of CABG patients that require resternotomy for bleeding has a coagulopathy masked a surgical cause of bleeding at the time of first closure.
In using aspirin to reduce the risks that CABG patients are exposed to, we are left trying to balance two conflicting goals, the prevention of thrombosis and the minimizing of hemorrhage. Logic alone is no longer sufficiently helpful and we need evidence to base our judgements on. Aspirin has long been established as a means of reducing graft occlusion rates following CABG. Goldman et al. were able to demonstrate improved graft survival at 9 days and at one year with a range of different doses of aspirin.2 The evidence that aspirin causes increased bleeding in CABG is also long-standing, if a little more disputed. Bashein et al. in a case controlled study found that aspirin use in the seven days leading up to CABG increased the blood loss, transfusion rates and the rate of resternotomy for bleeding.3 In a large (351 patients), randomized, double blind, placebo controlled trial, Goldman et al. specifically addressed the issue of when to start the aspirin. Both groups received postoperative aspirin, commencing at six hours. Their aspirin group also received aspirin preoperatively whereas the control patients were given placebo preoperatively. They also found an increase in bleeding and resternotomy rates in the group on preoperative aspirin. There was no difference in early graft patency rates between the two groups and they concluded that preoperative aspirin use conferred no advantage over its early institution postoperatively.4 More recently in a retrospective analysis of 2606 patients Ferraris et al. have also concluded that preoperative aspirin use is associated with a higher transfusion rate and rate of reoperation for bleeding.5
To be fair there are studies that have shown aspirin not to increase bleeding in CABG patients. In a prospective observational study that included 144 patients undergoing first time CABG Vuylsteke found no difference in bleeding complications.6 Rawitscher et al. conducted an observational study in 100 consecutive elective CABG procedures and concluded similarly.7 Tuman et al. similarly found no difference in their observational study in 317 cases of reoperative CABG, but all patients here received aminocaproic acid.8 The evidence that preoperative aspirin does cause bleeding problems in CABG patients is stronger, and should not be ignored. The number of studies that have examined the mitigating effects of aprotinin and tranexamic acid on this bleeding are indirect testimony that I am not alone in this view.9, 10, 11, 12, 13, 14, 15 Aspirin is known to exert its effect on platelet hemostatic function by the inhibition of the cyclooxygenase pathway. Tabuchi et al. have demonstrated that during bypass, platelets exposed to aspirin are more vulnerable to their shear-induced pathway being compromised than are normal platelets.16 This would explain why the timing of aspirin therapy is important (pre or post bypass) and might also explain why the bleeding problems associated with preoperative aspirin have not been demonstrated in CABG cases performed off bypass.17
The value of aspirin in protecting graft patency as already stated is beyond dispute. Dacey et al., in a case controlled study found that the use of preoperative aspirin reduced overall mortality in CABG patients but the nature of this study would not have picked out patients commencing aspirin early postoperatively from those starting it late.18 Mangano's paper is compelling in its presentation of the other benefits of this inexpensive drug in CABG patients. His study was prospective, multi-centred, large (N=5065) and observational focusing on early postoperative aspirin use and its association with fatal and non-fatal outcomes. Aspirin use within 48 hours postoperatively was associated with very significant reductions in mortality, as well as the incidence of stroke, renal failure and bowel infarction.19 His recommendation that early postoperative aspirin use be considered for all CABG patients unless specifically contraindicated is entirely reasonable.
The evidence that preoperative aspirin increases the rate of bleeding complications in on pump CABG patients is strong. The evidence that preoperative aspirin confers any advantages over its early institution postoperatively in these patients is poor or absent. While the dangers associated with preoperative aspirin use are not such as to warrant delaying urgent CABG surgery, they warrant the discontinuation of aspirin for seven days prior to elective procedures. The early institution of aspirin therapy after CABG surgery should be routine (unless contraindicated specifically) and in Mangano's data it was not associated with worse bleeding complications. The reverse was the case.
- Unsworth-White M J, Herriot A, et al. Resternotomy for bleeding after cardiac operation: a marker for increased morbidity and mortality. Ann Thor Surg 1995; 59:664-7.
- Goldman S, Copeland J, et al. Saphenous vein graft patency 1 year after coronary artery bypass surgery and effects of antiplatelet therapy. Results of a Veterans Administration Cooperative Study. Circulation 1989; 80: 1190-7
- Bashein G, Nessly M L, et al. Preoperative aspirin therapy and reoperation for bleeding after coronary artery bypass surgery. Arch Intern Med 1991; 151: 89-93.
- Goldman S, Copeland J, et al. Starting aspirin therapy after operation. Effects on early graft patency. Department of Veterans Affairs Cooperative Study Group. Circulation 1991; 84: 520-6
- Ferraris V A, Ferraris S P, et al. Aspirin and postoperative bleeding after coronary artery bypass grafting. Ann Surg 2002; 235: 820-7.
- Vuylsteke A, Oduro A, et al. Effect of aspirin on coronary artery bypass grafting. J Cardiothor Vasc Anesth 1997; 11: 832-4.
- Rawitscher R E, Jones J W, et al. A prospective study of aspirin.s effect on red blood cell loss in cardiac surgery. J Cardiovasc Surg 1991; 32: 1-7.
- Tuman K J, McCarthy R J, et al. Aspirin does not increase allogeneic blood transfusion in reoperative coronary artery surgery. Anesth Analg 1996; 83: 1178-84.
- Murkin J M, Lux J, et al. Aprotinin significantly decreases bleeding and transfusion requirements in patients receiving aspirin and undergoing cardiac operations. J Thor Cardiovas Surg 1994; 107: 554-61.
- Ivert T, Intonti M, et al. Effects of aprotinin during cardiopulmonary bypass in patients treated with acetylsalicylic acid. Scand Cardiovas J 1998; 32: 289-95.
- Klein M, Keith P R, et al. Aprotinin counterbalances an increased risk of perioperative hemorrhage in CABG patients pre-treated with Aspirin. Eur J Cardiothor Surg. 1998; 14: 360-6.
- Bidstrup B P, Hunt B J, et al. Amelioration of the bleeding tendency of preoperative aspirin after aortocoronary bypass grafting. Ann Thor Surg 2000; 69: 541-7.
- Moran S V, Lema G, et al. Comparison of two doses of aprotinin in patients receiving aspirin before coronary bypass surgery. Perfusion 2000; 15 : 105-110.
- Alvarez J M, Jackson L R, et al. 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 Thor Cardiovas Surg 2001; 122: 457-63.
- Pleym H, Stenseth R, 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.
- Tabuchi N, Huet R C, et al. Hemostatic function of aspirin-treated platelets vulnerable to cardiopulmonary bypass. Altered shear induced pathway. J Thor Cardiovasc Surg 1995; 110: 813-8.
- Srinivasan A K, Grayson A D, et al. Effect of preoperative aspirin use in off pump coronary artery bypass operations. Ann Thor Surg 2003; 76: 41-5.
- Dacey L J, Munoz J J, et al. Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients. Ann Thor Surg 2000; 70: 1986-90.
- Mangano D T, For the Multicenter Study of Perioperative Ischaemia Research Group. Aspirin and mortality from coronary bypass surgery. N Engl J Med 2002; 347: 1309-17.