Key Points:
- Saphenous vein graft (SVG) failure is common after coronary artery bypass grafting (CABG), with an occlusion rates of 20% within the first year after surgery.
- The role of LDL-cholesterol (LDL-C) lowering in preventing SVG failure is uncertain.
- NEWTON-CABG Cardiolink 5 found that starting evolocumab with 21 days of CABG in addition to background statin therapy did not improve SVG patency at 2 years compared to placebo, despite substantial additional LDL-C lowering.
- Further research is required to identify therapies that reduce the risk of SVG failure.
Preventing SVG failure after CABG remains a persistent challenge. While LDL-C is a causal contributor to native vessel atherosclerosis, the role of aggressive LDL-C lowering to improve SVG patency is uncertain.
On September 1st 2025, the results of “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” were presented at the European Society of Cardiology Congress in Madrid, Spain, with simultaneous publication in Lancet. The purpose of this study was to determine whether early, intensive LDL-C lowering with evolocumab reduces SVG failure after CABG.
This double-blind, multi-national trial randomized adults aged ≥ 18 years who underwent CABG with at least 2 SVGs to receive evolocumab 140mg subcutaneously or placebo within 21 days of surgery in addition to background moderate to high intensity statin therapy. The primary endpoint was the proportion of SVGs with ≥ 50% occlusion on coronary CT angiogram (CCTA) or clinically indicated invasive coronary angiography (ICA) at 24 months, referred to as the “vein graft disease rate” or VGDR.
Overall, 782 adults with randomized, 389 to evolocumab and 393 to placebo, however only 554 participants had primary outcome data available, 281 in the evolocumab group and 273 in the placebo group. In the modified intention to treat analysis of the participants with outcome ascertainment, the mean age was 66 years, 15% were female, and the median LDL-C was 70mg/dL in both groups. As expected, the evolocumab group experienced substantial LDL-C lowering compared to placebo (mean placebo adjusted LDL-C reduction at 24 months -48.4% [95% CI: -57.7, -39.1]). However, there was no significant difference in primary outcome: 24-month VDGR was 21.7% (149 of 686 grafts) in the evolocumab group and 19.7% (127 of 644 grafts) in the placebo group, for an absolute difference of 2.0 percentage points (95% CI: -3.1, 7.1; p = 0.44). There was also no significant difference between evolocumab and placebo in the key secondary endpoints of percentage of totally occluded SVGs (17% vs. 16%, respectively) or the proportion of patients with at least one totally occluded SVGs (30% vs. 28%, respectively). No safety signals were noted.
Prof. Subodh Verma of St. Michael’s Hospital, Toronto, Canada, 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, remodeling, 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.”
