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Review

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

^a Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn, Germany
^b Heinrich-Heine – University, Department of Thoracic and Cardiovascular Surgery, Moorenstrasse 5, D-40225 Duesseldorf, Germany
^c Heinrich-Heine – University, Department of Pharmacology and Clinical Pharmacology, Moorenstrasse 5, D-40225 Duesseldorf, Germany

Received 14 February 2008; received in revised form 10 March 2008; accepted 19 March 2008.

^_* Corresponding author. Tel.: +49 228 207 3136; fax: +49 228 207 3558. (Email: nzimmermann{at}bfarm.de).

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.

Abbreviations: ACS = acute coronary syndrome • ADP = adenosine diphosphate • ASA = aspirin • bid = twice daily (dosing) • CABG = coronary artery bypass graft surgery • CAD = coronary artery disease • CAPRIE = clopidogrel versus aspirin in patients at risk of ischaemic events • CHARISMA = clopidogrel for high atherothrombotic risk and ischaemic stabilisation, management and avoidance • CI = confidence interval • Clo = clopidogrel • COX = cyclooxygenase • CPB = cardiopulmonary bypass • CREDO = clopidogrel for the reduction of events during observation • CURE = clopidogrel in unstable angina to prevent recurrent ischaemic events • e.g. = for example (Latin abbreviation for exempli gratia) • HR = hazard ratio • i.e. = that is (Latin abbreviation for id est) • IMA = internal mammary artery • LTA = light transmission aggregation (turbidimetry) • MI = myocardial infarction • n.a. = not available • n.s. = not significant • NSAID = nonsteroidal anti-inflammatory drug • OPCAB = off-pump coronary artery bypass surgery • OR = odds ratio • qd = once daily (dosing) • PAD = peripheral arterial disease • PCI = percutaneous coronary intervention • PFA-100 = platelet function analyser • RR = relative risk • STEMI = ST-elevation myocardial infarction • SVG = saphenous vein graft • TIA = transient ischaemic attack • tid = three times daily (dosing) • TX = thromboxane • VK-A = vitamin K-antagonist

Key Words: Coronary artery bypass grafting • Platelet function • Antithrombotic therapy • Aspirin resistance • Aspirin nonresponse • Clinical outcome