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.” 

ENDS