Optimizing apoB levels improves plaque stabilization after ACS

In a post-hoc analysis of HUYGENS among statin-treated NSTEMI patients receiving evolocumab or placebo for 52 weeks, achievement of the apoB goal (<65 mg/dL) was associated with coronary plaque stabilization on imaging.

This summary is based on the publication of Fujino M, Di Giovanni G, Butters J, et al. - Achieved levels of apolipoprotein B and plaque composition after acute coronary syndromes: Insights from HUYGENS. Atherosclerosis. 2025 Feb 20;403:119145. doi: 10.1016/j.atherosclerosis.2025.119145.

Introduction and methods

Background

Measurement of apoB levels may improve the assessment of residual risk in patients with a history of CVD receiving lipid-lowering therapy [1,2]. The European Society of Cardiology (ESC) Guidelines on CVD prevention in clinical practice recommend apoB <65 mg/dL, in combination with aiming for LDL-c <55 mg/dL [3]. However, there is little knowledge on whether apoB contributes to the residual risk associated with vulnerable plaque lesions in patients with ACS.

The HUYGENS (High-Resolution Assessment of Coronary Plaques in a Global Evolocumab Randomized Study) trial demonstrated that evolocumab, in addition to statin therapy, resulted in favorable changes consistent with coronary plaque stabilization in patients with NSTEMI, compared with placebo [4].

Aim of the study

In a post-hoc analysis of the HUYGENS trial, the authors investigated the association between achievement of apoB target levels and plaque stabilization in post-ACS patients treated with evolocumab versus placebo in addition to statin therapy.

Methods

The HUYGENS trial was an international, multicenter, double-blind, placebo-controlled, phase 3 RCT in which 164 patients undergoing clinically indicated coronary angiography for NSTEMI, with interventional treatment of the culprit plaque, were randomized to subcutaneous evolocumab 420 mg monthly or placebo for 52 weeks. Inclusion criteria included angiographic stenosis ≥20% in a nonculprit vessel and elevated LDL-c levels (dependent on the use of statin therapy). All patients were scheduled to receive maximum-tolerated statin therapy. Participants underwent optical coherence tomography (OCT) in a nonculprit vessel at baseline and 50 weeks. Serial OCT imaging and apoB measurements were available for 112 patients.

Main results

• Patients who achieved the ESC-recommended apoB goal (<65 mg/dL) at follow-up (n=67; 59.8%) showed a greater mean ± SD increase in minimum fibrous cap thickness (FCT) from baseline to 50-week follow-up than those not achieving the apoB goal (n=45; 40.2%) (44.6 ± 36.0 vs. 24.9 ± 38.1 μm; P=0.007) and were more likely to experience any increase in minimum FCT (95.5% vs. 80.0%; P=0.002).
• Patients achieving the apoB goal also had a larger mean ± SD decrease in the lipid arc at follow-up compared with those not achieving the goal (–57.8 ± 52.8° vs. –27.0 ± 59.2°; P=0.005) and were more likely to demonstrate any decrease in the lipid arc (86.6% vs. 60.0%; P=0.001).
• Of the 67 patients who achieved the apoB goal, 6 (9.0%) had a thin-cap fibroatheroma (TCFA) at follow-up, compared with 18/45 patients (40.0%) not achieving the goal (P<0.001).
• Univariate analysis indicated the use of evolocumab (OR: 0.33; 95%CI: 0.12–0.83; P=0.003) and achievement of the apoB goal (OR: 0.14; 95%CI: 0.05–0.38; P<0.001) were associated with lower odds of the presence of a TCFA at follow-up.
• In multivariate analysis adjusted for age, female sex, and known risk factors, achievement of the apoB goal at follow-up was associated with the absence of a TCFA at follow-up (OR: 0.15; 95%CI: 0.03–0.55; P=0.004).

Conclusion

In this post-hoc analysis of the HUYGENS trial among NSTEMI patients treated with evolocumab versus placebo for 52 weeks, in addition to maximum-tolerated statin therapy, achievement of the apoB goal (<65 mg/dL) was associated with coronary plaque stabilization, as shown by a greater increase in minimum FCT and larger reduction in lipid arc, in a nonculprit vessel. Patients achieving the apoB goal were less likely to have a TCFA at follow-up than those not achieving the goal. “Given the dynamic nature of fibrous cap and lipid cores observed in post-ACS patients, our results highlight the potential benefit of immediate initiation of potent apoB-lowering therapy,” according to the authors.

Find this article online at Atherosclerosis.

References

1. C. Kohli-Lynch, G. Thanassoulis, M. Pencina, et al., The causal-benefit model to prevent cardiovascular events, JACC (J. Am. Coll. Cardiol.): Advances 3 (2024).
2. N.A. Marston, R.P. Giugliano, G.E.M. Melloni, et al., Association of apolipoprotein B-containing lipoproteins and risk of myocardial infarction in individuals with and without atherosclerosis: distinguishing between particle concentration, type, and content, JAMA Cardiol 7 (2022) 250–256.
3. F.L.J. Visseren, F. Mach, Y.M. Smulders, et al., ESC Guidelines on cardiovascular disease prevention in clinical practice, Eur. Heart J. 42 (2021) 3227–3337, 2021.
4. S.J. Nicholls, Y. Kataoka, S.E. Nissen, et al., Effect of evolocumab on coronary plaque phenotype and burden in statin-treated patients following myocardial infarction, JACC Cardiovasc Imaging 15 (2022) 1308–1321.