Effects of Aspirin Responsiveness and Platelet Reactivity on Early Vein Graft Thrombosis After Coronary Artery Bypass Graft Surgery

Objectives The purpose of this study was to determine if an incomplete response to or inadequate antiplatelet effect of aspirin, or both, contribute to saphenous vein graft (SVG) occlusion after coronary artery bypass graft (CABG) surgery. Background Thrombosis is the predominant cause of early SVG occlusion. Aspirin, which inhibits cyclooxygenase-1 activity and thromboxane generation in platelets, reduces early SVG occlusion by one-half. Methods Aspirin responsiveness and platelet reactivity were characterized 3 days and 6 months after coronary artery bypass graft surgery in 229 subjects receiving aspirin monotherapy by platelet aggregation to arachidonic acid, adenosine diphosphate, collagen and epinephrine, Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Newark, Delaware) closure time (CT) using collagen/epinephrine agonist cartridge and collagen/adenosine diphosphate (CADP) agonist cartridge, VerifyNow Aspirin assay (Accumetrics, Inc., San Diego, California), and urine levels of 11-dehydro-thromboxane B-2 (UTXB2). 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 CADP CT measured 6 months after surgery correlated with outcome. By multivariate analysis, CADP CT of <= 88 s (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 Aspirin-insensitive thromboxane generation measured by UTXB2 and shear-dependent platelet hyper-reactivity measured by Platelet Function Analyzer-100 CADP CT are novel independent risk factors for early SVG thrombosis after coronary artery bypass graft surgery. (J Am Coll Cardiol 2011; 57:1069-77) (C) 2011 by the American College of Cardiology Foundation