1) The need for antiplatelet therapy in CABG
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.
2) Timing of antiplatelet therapy
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).
4) Treatment interruption
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).