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

Abstract

Objectives To determine if an incomplete response to and/or inadequate antiplatelet effect of aspirin 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 half. Methods Aspirin-responsiveness and platelet reactivity were characterized 3 days and 6 months after CABG in 229 subjects on aspirin monotherapy by; platelet aggregation to arachidonic acid, ADP, collagen and epinephrine; PFA-100 closure time (CT) using collagen/epinephrine (CEPI) and collagen/ADP (CADP) agonist cartridges; VerifyNow Aspirin assay, and; urine levels of 11-dehydro-thromboxane B2 (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 PFA-100 CADP CT measured 6 months after surgery correlated with outcome. By multivariate analysis, CADP CT ≤88 seconds (OR 2.85, P=0.006), target vessel diameter ≤1.5 mm (OR 2.38, P=0.01) and UTXB2 ≥450 pg/mg creatinine (OR 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 PFA-100 CADP CT are novel independent risk factors for early SVG thrombosis after CABG surgery.

Urinary 11‐Dehydro‐Thromboxane B 2 as a Predictor of Acute Myocardial Infarction Outcomes: Results of Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) Study

“…The latter is a stable metabolite excreted in urine, and its measurement provides a reliable estimate of the total in vivo production of TXA 2 including the extraplatelet sources 7, 8. 11‐Dehydro‐TXB 2 has been found to be elevated in several atherothrombotic diseases and to correlate with major adverse clinical events 9, 10, 11, 12, 13, 14. However, none of the studies have evaluated the association of 11‐dehydro‐TXB 2 with patients’ long‐term outcomes in AMI.…”

Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639)

“…Thromboxane generation (increased levels of urinary 11-dehydro thromboxane B2) and shear-dependent platelet hyper-reactivity were independent risk factors for early saphenous vein graft thrombosis after CABG 33 .…”

“…Gluckman et al evaluated effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis after CABG 33 . Thromboxane generation (increased levels of urinary 11-dehydro thromboxane B2) and shear-dependent platelet hyper-reactivity were independent risk factors for early saphenous vein graft thrombosis after CABG 33 .…”

Conduit Selection for Improved Outcomes in Coronary Artery Bypass Surgery

“…In addition, early vein graft failure is associated with increased perioperative myocardial infarction [10,61], which consequently affects survival after CABG [58,59]. Several potential explanations exist for the recently chronicled poor performance of RSVG as aorto-coronary conduits including early technical errors, endothelial injury, and early thrombosis, which may be related to insufficient biologic reaction to aspirin or inadequate antiplatelet effect of aspirin [62][63][64]. One important contributor to poor RSVG conduit performance, receiving significant recent attention, may be the practice of harvesting the conduit endoscopically (EVH).…”