Effect of Evolocumab on Grafts Post-Coronary Artery Bypass Surgery: Post-Hoc Analysis of Newton-CABG CardioLink-5.

BACKGROUND: Graft failure remains a significant clinical problem. OBJECTIVES: This study aimed to evaluate effects of evolocumab on graft failure, stenosis severity, stenosis types, and plaque burden in saphenous vein grafts (SVGs), internal mammary artery (IMA), and radial artery grafts using coronary computed tomography angiography (CCTA). METHODS: Analysis of the randomized NEWTON-CABG CardioLink-5 trial was undertaken in evaluable grafts 24 months postsurgery. Graft stenosis was graded normal: <20%, moderate: 20% to <50%, or graft failure: 50% to 100%. Stenoses ≥20% were classified: positive remodeling, >25% low-attenuation plaque (LAP), or spotty calcification. Plaque burden (calcified, mixed, or LAP) was measured. RESULTS: We studied 1,275 SVGs, 514 IMA grafts, and 39 radial artery grafts. There were no differences between treatment groups for graft failure in any graft type. Evolocumab had a lower percentage of moderate lesions among SVGs (11.5% vs 19.3%, P < 0.001), a similar nonsignificant trend in IMA grafts (3.5% vs 5.9%), and fewer focal stenoses ≥20% showing positive remodeling, >25% LAP, or spotty calcification. SVGs accumulated more plaque burden but with greater percentage calcified (P < 0.002) and mixed plaque (P < 0.001) and less percentage LAP (P < 0.001) than IMA grafts. CONCLUSIONS: Evolocumab did not improve early graft failure, but exploratory results suggest that it may diminish moderate stenoses in SVGs and stenoses with unfavorable features. SVGs accumulated more plaque burden than IMA grafts but with less percentage LAP, possibly due to the early arterialization process involving smooth muscle cell proliferation, neointimal hyperplasia, and extracellular matrix expansion affecting only the SVGs.