Aspirin in coronary artery bypass surgery: new aspects of and alternatives for an old antithrombotic agent

Abstract

The success of coronary artery bypass graft surgery (CABG) depends mainly on the patency of the graft vessels. Aortocoronary vein graft disease is comprised of three distinct but interrelated pathological processes: thrombosis, intimal hyperplasia and atherosclerosis. Early thrombosis is a major cause of vein graft attrition during the first month after CABG, while during the remainder of the first year, intimal hyperplasia forms a template for subsequent atherogenesis, which thereafter predominates. Platelets play a crucial role in the pathophysiology of graft thrombosis and aspirin is the primary antiplatelet drug that has been shown to improve vein graft patency within the first year after CABG. Nevertheless, a significant number of grafts still occlude in the early postoperative period despite 'appropriate' aspirin treatment. Moreover, laboratory investigations showed that the expected inhibition of platelet function is not always achieved. This has been called 'aspirin nonresponse' or 'aspirin resistance', although a uniform definition is lacking. The finding that a considerable number of patients show an impaired antiplatelet effect of aspirin after CABG brought new insight into the discussion concerning poor patency rates of bypass grafts: the early period after CABG shows a coincidence of an increased risk for bypass thrombosis (amongst others, due to platelet activation and endothelial cell disruption of the graft) and an increased prevalence of aspirin resistance. Hitherto, the underlying mechanisms of aspirin resistance are uncertain and largely hypothetical; amongst others, increased platelet turnover, enhanced platelet reactivity, systemic inflammation, and drug-drug interaction are discussed. Up to now available data concerning the clinical outcome of aspirin resistant CABG patients are limited, and there is evidence that platelets of patients with graft thrombosis are more likely to be resistant to aspirin compared with patients without thrombotic events. Many publications concerning aspirin resistance are available today, but reports addressing this topic in CABG patients are sparse. This review summarises recent insights into the antiplatelet treatment after CABG and describes the clinical benefit, but also the therapeutic failure of the well-established drug aspirin. Moreover, possible pharmacological approaches to improve antithrombotic therapy in aspirin nonresponders among CABG patients are discussed.

Aspirin Resistance: Current Status and Role of Tailored Therapy

“…64 Aspirin has been shown to have beneficial effects on vein graft patency for the first year following CABG. 65 Up to two-thirds of patients are aspirin resistant, as assessed by arachidonic acid-mediated platelet aggregation, following CABG, especially within the first 10 days following surgery.…”

“…65 Up to two-thirds of patients are aspirin resistant, as assessed by arachidonic acid-mediated platelet aggregation, following CABG, especially within the first 10 days following surgery. 64 Traditional, on-pump cardiopulmonary bypass leads to a decline in circulating platelet count by as much as 30% to 50%. This leads to increased platelet turnover and the counts often recover or surpass preoperative levels by postoperative day 10.…”

“…67 As well, platelets are more responsive to aspirin after off-pump coronary surgery compared to on-pump surgery although aspirin resistance has been described in the offpump surgical population. 64 Wang et al 68 found that 29.7% of their cohort of off-pump surgery patients was aspirin resistant, using arachidonic acid-mediated platelet aggregometry, on postoperative day 1 and only 4.5% remained resistant on postoperative day 10. All patients were aspirin sensitive by 6 months of follow up.…”

“…69 Likewise, more frequent aspirin dosing was no more efficacious than once-daily dosing. 64 as an antithrombotic agent. For the majority of patients, aspirin appears to lack dose-responsiveness in its antithrombotic effects but does demonstrate dose-dependence for its side effects, notably gastrointestinal bleeding.…”

Secondary prevention for CABG patients: take two arterial grafts at the time of your coronary operation

“…As part of the wide spectrum of patients with ischemic heart disease, aspirin plays a key role also in the cohort of those undergoing coronary artery bypass grafting (CABG) surgery. Vein graft patency has in fact been demonstrated to be strongly influenced by aspirin, with angiographically detected vein graft occlusion occurring up to five times more frequently in patients receiving placebo than in those receiving acetylsalicylic acid (5). Aspirin administration shortly after CABG has been proved to improve survival by reducing the burden of ischemic events (6) and, accordingly, international guidelines recommend aspirin to be initiated within 6-12 hours postoperatively, if not administered preoperatively (7,8).…”