Lower achieved LDL-c level after CABG associated with improved vein graft outcomes

In a post-hoc analysis of NEWTON-CABG CardioLink-5 among post-CABG patients, both a lower LDL-c level at 3 months and larger LDL-reduction were associated with less saphenous vein graft stenosis or occlusion at 24 months.

This summary is based on the publication of Szarek M, Leiter LA, Teoh H, et al. - Relationship Between Achieved LDL-C and Saphenous Vein Graft Patency: A Post Hoc Analysis of the NEWTON-CABG CardioLink-5 Study. Eur J Prev Cardiol. 2026 Mar 31:zwag190 [Online ahead of print]. doi: 10.1093/eurjpc/zwag190

Introduction and methods

Background

Despite improvements in the patency of saphenous vein grafts (SVGs) in the last decades [1], SVG failure is still common. Intensive LDL-c reduction reduces the risk of CV events in patients with a history of CABG [2,3], and it could potentially improve SVG patency. However, in the recent NEWTON-CABG CardioLink-5 (Effect of Evolocumab on Saphenous Vein Graft Patency Following Coronary Artery Bypass Surgery) trial, treatment with evolocumab, in addition to moderate- to high-intensity statin therapy, did not change SVG patency or any other measures of SVG disease compared with placebo at 24 months after CABG [4].

Aim of the study

In a post-hoc analysis of the NEWTON-CABG CardioLink-5 trial, the authors investigated whether achieved LDL-c and non-HDL-c levels at 3 months are related to subsequent SVG patency and plaque volume in post-CABG patients, regardless of treatment assignment.

Methods

The NEWTON-CABG CardioLink-5 trial was a multinational, multicenter, investigator-initiated, double-blind, placebo-controlled, parallel-group, phase 4 RCT in which 782 adults (≥18 years) on moderate- to high-intensity statin therapy and who were scheduled to undergo CABG surgery with ≥2 SVGs were enrolled. At 3–21 days after the index CABG, participants were randomized to subcutaneous evolocumab 140 mg or placebo every 2 weeks for 24 months. In the current analysis, 499 patients with LDL-c measurements at 3 months and ≥1 evaluable SVGs at 24 months were included (1198 SVGs in total).

Outcomes

The primary endpoint was the SVG disease rate, defined as the proportion of SVGs with ≥50% stenosis or total occlusion on coronary CT angiography or clinically indicated invasive angiography at 24 months. Secondary efficacy endpoints included the proportion of totally occluded (i.e., 100%) SVGs, proportion of participants with ≥1 totally occluded SVGs, and SVG total plaque volume.

Main results

• Mean ± SD LDL-c level decreased from 2.04 ± 1.10 mmol/L at baseline to 1.03 ± 0.75 mmol/L at 3 months (mean ± SD change: –0.99 ± 1.16 mmol/L).
• The LDL-c level achieved at 3 months was associated with the primary endpoint of SVG disease rate (OR per 1 mmol/L decrement: 0.74; 95%CI: 0.61–0.91; P=0.005). There was no interaction with treatment assignment (P for interaction=0.79).
• LDL-c change from baseline to 3 months was also related to the primary endpoint (OR per 1 mmol/L decrease: 0.78; 95%CI: 0.63–0.98; P=0.03; P for interaction with treatment=0.84).
• Similar associations were found for SVG total occlusion rate and the proportion of participants with ≥1 totally occluded SVGs.
• Achieved LDL-c level at 3 months was not related to the mean change in total plaque volume (–0.10 mm³ per 1 mmol/L decrement; 95%CI: –0.34 to 0.15; P=0.45; P for interaction with treatment=0.07).
• In the overall analysis cohort, LDL-c change from baseline to 3 months was not associated with mean total plaque volume change (0.01 mm³ per 1 mmol/L decrease; 95%CI: –0.25 to 0.27; P=0.94), although there was significant interaction with treatment assignment (P for interaction=0.02).

Conclusion

This post-hoc analysis of the NEWTON-CABG CardioLink-5 trial, in which patients on moderate- to high-intensity statin therapy undergoing CABG were randomized to evolocumab or placebo, indicated that both a lower LDL-c level at 3 months and a larger LDL-reduction from baseline to 3 months were associated with a reduced SVG disease rate at 24 months, independent of treatment assignment.

The authors conclude their “findings suggest that LDL-c concentrations may have some function in SVG patency regardless of the mechanism(s) for lowering them. These results also underscore the importance of adhering to cholesterol guidelines following CABG.”

Find this article online at Eur J Prev Cardiol.

References

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