NEWTON-CABG: Aiming for improved SVG patency with PCSK9 inhibitors

Early addition of evolocumab to moderate- to high-intensity statin therapy did not improve saphenous vein graft (SVG) patency in patients undergoing coronary artery bypass grafting (CABG), according to the primary results of the NEWTON-CABG CardioLink-5 trial.

The NEWTON-CABG CardioLink-5 (NCT03900026) study assessed whether the PCSK9 inhibitor evolocumab, an LDL-cholesterol-lowering agent, could reduce 2-year SVG failure rates in patients who underwent CABG and received moderate- to high-intensity statins. Dr Subodh Verma (University of Toronto, ON, Canada) and colleagues randomised 782 adult participants after recent CABG with at least 2 SVGs and already receiving statin therapy 1:1 to evolocumab, 140 mg, every 2 weeks, or to placebo [1]. “Of note, there was no LDL-cholesterol entry criterion,” emphasised Dr Verma. The primary endpoint was vein graft disease rate, defined as the proportion of SVGs with significant stenosis (≥50%) or total occlusion on ≥64-slice coronary computed tomography angiography, or clinically indicated coronary angiography at 24 months of follow-up.

As expected, evolocumab lowered LDL cholesterol compared with placebo (-52.4% vs -4.0%). However, the primary endpoint was not met. The rate of primary outcome events was 19.7% in the placebo arm and 21.7% in the evolocumab arm (OR 1.13; 95% CI 0.83-1.54; P=0.44). Secondary efficacy outcomes did not indicate that evolocumab improved clinical outcomes in these patients at 24 months either.

“The findings suggest that early SVG failure is mechanistically different from native coronary atherosclerosis,” concluded Dr Verma. “We need new biological targets and mechanistic interventions to deal with the persistent problem of SVG failure.”

1. Verma S, et al. Randomized trial of evolocumab on saphenous vein graft patency following coronary artery bypass surgery: the NEWTON-CABG CardioLink-5 Trial. Hotline 10, ESC Congress 2025, 29 August–1 September, Madrid, Spain.

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Posted on 7 November 20257 November 2025