Key take-aways
- Saphenous vein graft failure remains a persistent clinical problem following coronary artery bypass grafting (CABG).
- In the NEWTON-CABG CardioLink-5 trial, cholesterol-lowering with evolocumab did not reduce saphenous vein graft disease in the 2 years following CABG compared with placebo.
- Further research is needed to develop novel strategies to improve on the current high rates of graft failure.
Madrid, Spain – 1 September 2025: After coronary artery bypass grafting (CABG), evolocumab did not reduce saphenous vein graft disease rates at 2 years compared with placebo, according to late-breaking research presented in a Hot Line session today at ESC Congress 2025.1
CABG remains one of the most commonly performed cardiac surgical procedures worldwide and saphenous vein grafts are used in almost all these procedures. However, graft failure remains a persistent problem – up to 20% of grafts fail within the first year and nearly half are occluded within 10 years after surgery.2
"Low-density lipoprotein cholesterol (LDL-C) is a recognised causal factor in arterial atherosclerosis and cardiovascular risk; however, evidence linking LDL-C-lowering therapies to vein graft patency is sparse and inconsistent. We investigated whether intensive LDL-C lowering with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor could improve early saphenous vein graft failure after CABG," explained Principal Investigator, Professor Subodh Verma from St. Michael's Hospital, Toronto, Canada.
NEWTON-CABG CardioLink-5 was an investigator-initiated, double-blind, randomised, placebo-controlled trial conducted in Canada, Australia, Hungary and the USA. The main inclusion criteria were age ≥18 years, CABG surgery with at least two saphenous vein grafts and treatment with moderate-to-high-intensity statin therapy. Patients were randomised 1:1 postoperatively (3–21 days after CABG) to subcutaneous evolocumab 140 mg or placebo every 2 weeks. The primary endpoint was the 24-month vein graft disease rate (the proportion of grafts with ≥50% occlusion on coronary computed tomography angiography or clinically indicated invasive angiography) in the modified intention-to-treat population.
Among the 782 randomised participants, the median age was 66 years and 15% were female. The median LDL-C level was 1.9 mmol/l and evolocumab achieved a mean 48.4% placebo-adjusted LDL-C reduction at 24 months (−52.4% vs. −4.0%).
Regarding the primary endpoint, the 24-month vein graft disease rate was not significantly different between the groups: 21.7% with evolocumab and 19.7% with placebo (difference 2.0%; 95% confidence interval −3.1 to 7.1; p=0.44).
There were no significant differences between evolocumab and placebo in the key secondary efficacy endpoints of the percentage of totally occluded grafts at 24 months (17% vs. 16%, respectively) and the proportion of patients with at least one totally occluded grafts at 24 months (30% vs. 28%, respectively).
Treatment was well tolerated, with similar adverse event profiles between the groups.
Professor Verma concluded: "Evolocumab substantially lowered LDL-C levels but did not reduce vein graft disease rate at 2 years compared with placebo. While PCSK9 inhibitors continue to play an important role in secondary prevention in these patients, our findings suggest that further LDL-C lowering does not affect the pathophysiological mechanisms of early graft failure. Rather, remodelling, thrombotic and/or inflammatory processes may be responsible and further research is needed to develop novel approaches to reduce the current high rates of saphenous vein graft disease."
