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Effects of Aspirin Responsiveness and Platelet Reactivity on Early Vein Graft Thrombosis After Coronary Artery Bypass Graft Surgery
Study Questions:
What parameters of platelet function following coronary artery bypass graft surgery (CABG) in patients on aspirin (ASA) are predictive of early bypass graft failure?
Methods:
Aspirin responsiveness and platelet reactivity were characterized 3 days and 6 months after CABG in 229 subjects receiving ASA monotherapy by platelet aggregation to arachidonic acid, adenosine diphosphate (ADP), collagen and epinephrine, PFA-100 closure time (CT) using collagen/epinephrine diphosphate agonist cartridge and collagen/adenosine diphosphate (CADP) agonist cartridge, VerifyNow Aspirin assay (Accumetrics, Inc., San Diego, CA), and urine levels of 11-dehydro-thromboxane B2 (UTXB2). Saphenous vein graft (SVG) patency was determined 6 months after surgery by computed tomography coronary angiography.
Results:
Inhibited arachidonic acid-induced platelet aggregation, indicative of aspirin-mediated cyclooxygenase-1 suppression, occurred in 95% and >99% of subjects 3 days and 6 months after surgery, respectively. Despite this, 73% and 31% of subjects at these times had elevated UTXB2. Among tested parameters, only UTXB2 and PFA-100 CADP CT measured 6 months after surgery correlated with outcome. By multivariate analysis, CADP CT of ≤88 seconds (odds ratio, 2.85; p = 0.006), target vessel diameter of ≤1.5 mm (odds ratio, 2.38; p = 0.01), and UTXB2 of ≥450 pg/mg creatinine (odds ratio, 2.59; p = 0.015) correlated with SVG occlusion. CADP CT and UTXB2 in combination further identified subjects at particularly high and low risk for SVG occlusion.
Conclusions:
ASA-insensitive thromboxane generation measured by UTXB2 and shear-dependent platelet hyper-reactivity measured by PFA-100 CADP CT are novel independent risk factors for early SVG thrombosis after CABG.
Perspective:
Despite ASA therapy, early SVG closure is common as demonstrated in this study, in which 31% of patients experienced at least one occluded vein graft and 9% of patients lost all their SVGs when studied 6 months following surgery. Since early vein graft loss is likely due to thrombotic occlusion, more potent antithrombotic strategies may be beneficial, particularly if patients at high risk of graft closure can be identified. Whether addition of clopidogrel or other novel antithrombotic treatments will reduce this risk will require additional prospective study.
Keywords: Thromboxanes, Coronary Angiography, Platelet Function Tests, Thrombosis, Thromboxane B2, Platelet Aggregation, Saphenous Vein, Risk Factors, Blood Platelets, Collagen, Coronary Artery Bypass
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