Greater increase in minimum fibrous cap thickness by PCSK9i after NSTEMI

ESC 2021 Imaging findings from the HUYGENS study showed that increase in minimum fibrous cap thickness and decrease in the maximum lipid arc was greater after 12 months of evolocumab compared to placebo post-ACS.

Presented at the ESC congress 2021 by: Prof. Stephen Nicholls, MD, PhD Melbourne, Australia

Introduction and methods

Previous studies with IVUS have shown that high intensity statins with and without PCSK9 inhibitors result in plaque regression and that the degree of plaque regression was proportional to LDL-c lowering. Plaque vulnerability plays an important role in residual CV risk, but the impact of lipid lowering on plaque vulnerability is unknown.

In the HUYGENS study the impact of evolocumab on top of statin therapy on plaque phenotype was examined in patients post-ACS.

Patients with NSTEMI, angiographic CAD and qualifying LDL-c dependent on prior statin use, intend to be subsequently treated with maximally tolerated statin, target segment on optical coherence tomography (OCT) containing at least one image with fibrous cap thickness (FCT) <120 µm and one image with lip arc >90° were recruited. Patients were randomized to evolocumab 420 mg SC monthly or matching placebo, in addition to background lipid lowering therapy. Patients underwent OCT at baseline and at week 50. There were 135 patients who completed the study.

OCT analysis was performed on cross-sectional images 0.2 mm apart through a matched arterial segment. Analysis included measurement of the minimum FCT and extent of lipid arc in each image. Primary endpoint was the change in minimum FCT anywhere in the segment.

Main results

• The increase in the primary endpoint, the absolute change in minimum FCT anywhere throughout the segment, was greater in the evolocumab group (+42.7 µm) than in the placebo group (+21.5 µm) (P=0.015).
• Also, the percent change in minimum FCT anywhere throughout the segment was greater in the evolocumab group (+81.8%) than in the placebo group (+44.3%) (P=0.04).
• The mean minimum FCT in all images throughout the segment showed similar findings: change in FCT was +62.3 µm in the evolocumab group and +29.8 µm in the placebo group (P=0.02).
• The change in maximum lipid arc was greater in the evolocumab group (-57.5%) than in the placebo group (-31.4%) (P=0.04).
• An exploratory endpoint showed that the percentage patients with any image of on-treatment minimum FCT <65 µm (which is associated with increase propensity to plaque rupture) was lower in the evolocumab group (12.5%) than in the placebo group (30.2%).
• When pooling the treatment groups together showed that lower achieved LDL-c or greater absolute reduction in LDL-c were associated with greater thickening of the fibrous cap.
• Pre-specified analysis focused on changes in lipid rich plaques revealed similar benefits; greater increases for minimum FCT, maximum lipid arc and lipid length were observed in the evolocumab group.
• Evolocumab was well-tolerated without an increase in adverse events of specific interest.

Conclusion

In the HUYGENS study, addition of evolocumab to maximally tolerated statins for 12 months resulted in a greater increase in the minimum FCT and decreases in the maximum lipid arc, throughout the vessel and in lipid rich plaques, when compared to placebo on top of maximally tolerated statins. The degree of benefit on plaque phenotype was proportional to the intensity of lipid lowering.

Prof. Nicholls concluded that these findings suggest that vulnerable plaques can be stabilized after an ACS and this should motivate the use of intensive lipid lowering therapies in patients post-ACS.

- Our reporting is based on the information provided at the ESC Congress -

The rationale and design of this study were published in Cardiovasc Diagn Ther.