Effects of PCSK9i on coronary plaque morphology after 26 weeks in CAD patients
Effect Of Evolocumab On Coronary Plaque Characteristics In Stable Coronary Artery Disease: A Multimodality Imaging Study (the Yellow III Study)
Presented at the ACC.23 by: Annapoorna Kini, MD - New York, NY, USA
Introduction and methods
PCSK9 inhibitors have demonstrated to reduce the residual CV risk in patients with CAD. These observed CV benefits are associated with reduction in the percentage atheroma volume (PAV) determined by IVUS in patients with CAD in the GLAGOV study. Furthermore, an increase in minimum fibrous cap thickness (FCT) was observed by optical coherence tomography (OCT) in NSTEMI patients in the HUYGENS study. Last, in the PACMAN-AMI, a reduction of the maximal lipid core burden index within 4 mm (maxLCBI 4mm) was seen by NIRS.
Previous YELLOW studies have shown reduced maxLCBI 4 mm (YELLOW I) and increased FCT (YELLOW II) in obstructive lesions with rosuvastatin for 6-12 week in patients with CAD.
The aim of YELLOW III was to examine the effect of evolocumab on coronary plaque morphology using intravascular imaging (OCT and NIRS/IVUS) after 26 weeks in patients with stable CAD who were taking maximally tolerated statin therapy.
Patients with stable CAD who underwent cardiac catheterization and ≥4 weeks on max tolerated statin therapy were screened. Patients underwent PCI for a non-obstructive lesion (30-50% stenosis) identified by angiography in a non-culprit vessel and those with a lipid rich plaque (max lipid arc >90° and minimal FCT ≤120 µm assessed by OCT of the study lesion) were included (n=137) and underwent NIRS/IVUS of the study lesion at baseline, and at follow-up after 26 weeks of evolocumab (140 mg every 2 weeks). Those without a lipid rich plaque were excluded.
The primary endpoint was change in FCT assessed by OCT. The co-primary endpoint was change in maxLCBI 4 mm assessed by NIRS.
- Absolute change in minimal FCT was 26.8 ± 22.3 µm (P<0.001). The percentage of patients with FCT <65 µm decreased from 48% to 13%. The percentage of patients with increased fibrous cap was 80% at 26 weeks.
- Change in maxLCBI 4 mm was -93.7 ± 140.5 (P<0.001). The percentage of patients with decreased maxLCBI 4 mm at 26 weeks was 76%.
- Secondary imaging endpoints assessed by OCT – maximum lipid arc, average lipid arc, lipid length, lipid volume index, and macrophages and calcium markers- were all significantly changed after 26 weeks of evolocumab.
- Moreover, total atheroma volume was changed by -6.0 ± 12.5 mm3 (P<0.001), and the percent atheroma volume by -1.38 ± 1.48% (P<0.001).
- Last, absolute change in lesion LCBI was -49.6 ± 80.6 (P<0.001).
The YELLOW III study demonstrated that addition of evolocumab for 26 weeks to maximally tolerated statins in patients with CAD resulted in significant increase in minimum FCT as assessed by OCT, reduction in maxLCBI 4 mm by NIRS and reduction in atheroma volume by IVUS in non-obstructive lesions.
Annapoorna Kini noted that 20% of patients had no FCT thickening and 24% did not experience LCBI reduction. Gene expression analysis in peripheral blood mononuclear cells (PBMCs) -that was included in the study, but not yet presented- will allow to create predictive models to identify responders to PCKS9 inhibition with regard to plaque morphology.
- Our reporting is based on the information provided at the ACC.23/WCC -
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