Early and intensive lowering of LDL cholesterol (LDL-C) with evolocumab did not reduce saphenous vein graft (SVG) disease at 24 months for patients who had recently undergone coronary artery bypass graft (CABG) surgery, according to the results of the NEWTON-CABG CardioLink-5 trial.¹ Despite achieving a substantial reduction in LDL-C, the intervention showed no significant benefit over placebo in preventing graft failure, a persistent challenge in post-CABG care.²
NEWTON-CABG CardioLink-5 was an international, multicentre, randomised, double-blind, placebo-controlled trial conducted across 23 sites. The study enrolled 782 adults who had undergone CABG with at least two SVGs and were already receiving moderate- or high-intensity statin therapy.
Within 21 days of their surgery, participants were randomly assigned in a 1:1 ratio to receive either subcutaneous evolocumab 140 mg or a matching placebo every two weeks. The primary endpoint was the 24-month vein graft disease rate (VGDR), defined as the proportion of SVGs with 50% or greater occlusion, as assessed by coronary CT angiography or clinically indicated invasive angiography.
At baseline, the median LDL-C was 1.85 mmol/L in the evolocumab group and 1.86 mmol/L in the placebo group. Over the 24-month follow-up period, treatment with evolocumab resulted in a mean placebo-adjusted reduction in LDL-C of 48.4% (a 52.4% reduction in the evolocumab group vs a 4.0% reduction in the placebo group).
Despite this significant lipid lowering, the primary endpoint was not met. The 24-month VGDR was 21.7% (149 of 686 grafts) in the evolocumab group compared to 19.7% (127 of 644 grafts) in the placebo group. The difference of 2.0% was not statistically significant (95% CI –3.1 to 7.1; p=0.44). The treatment was well tolerated, and the safety profiles were similar between the two arms.
The findings from NEWTON-CABG suggest that while intensive LDL-C reduction is a cornerstone of secondary prevention for atherosclerosis, its role in preventing early SVG failure may be limited. The study authors concluded that, “Further LDL-C lowering does not appear to meaningfully affect the pathophysiological mechanisms responsible for early SVG failure.”¹ These results indicate that other mechanisms beyond LDL-C may be more dominant drivers of the early pathological changes that lead to SVG occlusion.
This study was funded by Amgen Canada.
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References
1. Verma S, Leiter LA, Teoh H, et al. Effect of evolocumab on saphenous vein graft patency after coronary artery bypass surgery (NEWTON-CABG CardioLink-5): an international, randomised, double-blind, placebo-controlled trial. Lancet. 2025. https://doi.org/10.1016/S0140-6736(25)01633-2.
2. Gaudino M, Antoniades C, Benedetto U, et al. Mechanisms, consequences, and prevention of coronary graft failure. Circulation. 2017;136:1749-1764. https://doi.org/10.1161/CIRCULATIONAHA.117.027597.