Abstract Body (Do not enter title and authors here): Background:
Saphenous vein graft (SVG) failure is a critical limitation for the long-term success of CABG surgery, with up to 30% of SVGs failing by 2 years. The NEWTON-CABG CardioLink-5 trial evaluated the effect of early evolocumab initiation on SVG patency 2 years post-surgery. Whether diabetes, a key driver of atherothrombosis, and a major determinant in surgical vs. percutaneous revascularization decision making, may modulate SVG disease progression is poorly defined. We report a pre-specified subgroup analysis evaluating SVG outcomes in patients with vs. without diabetes.
Methods:
NEWTON-CABG (NCT03900026) was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled patients within 3–21 days post-CABG surgery (≥2 SVGs) who were on moderate- to high-intensity statin therapy. There was no pre-specified LDL-C entry criterion. Participants were randomized 1:1 to receive evolocumab 140 mg or placebo every 2 weeks for 2 years. The primary endpoint was SVG disease rate (≥50% stenosis in any SVG by CCTA or clinically indicated invasive angiography) at 2 years. Key secondary endpoints included total occlusion rates and the proportion of patients with ≥1 occluded SVG. This pre-specified analysis evaluated the primary and secondary outcomes as well as comparative efficacy of evolocumab vs. placebo by baseline diabetes status.
Results:
Of the 782 patients (median age 66 years, ~15% women) enrolled across 4 countries, ~42% had diabetes at baseline. Key baseline characteristics are shown in the Table. The median time from CABG surgery to randomization was 13 days. Full results of the primary endpoint are embargoed until a Hot Line presentation at ESC 2025. The proposed AHA late-breaker will present new data on (a) SVG failure rates by baseline diabetes status and (b) the impact of evolocumab vs. placebo on various endpoints in patients with and without diabetes including subgroup-specific rates of ≥50% SVG stenosis, total occlusions, patient-level graft failure, a composite win ratio, and SVG plaque volume.
Conclusions:
NEWTON-CABG is the first randomized trial to assess the effect of intensive LDL-C lowering with a PCSK9 inhibitor initiated early after CABG on SVG patency. This pre-specified analysis will provide pivotal insights into whether diabetes is an independent risk factor for SVG failure and whether evolocumab modifies this risk. These findings will have important implications for the large cohort of post-CABG patients with diabetes.