Intra-coronary imaging before and after PCSK9 inhibition stratified by residual inflammatory risk: a serial imaging sub-study of YELLOW III
P C Revaiah, Y Vengrenyuk, V Krishna Santosh, M Karki, K Yasumura, J M. Sweeny, S Khera, V Kapur, A Hooda, P Krishnan, P R Moreno, R Mehran, J Narula, S K. Sharma, A S KiniAbstract
Background
Residual inflammatory risk (RIR) is an important determinant of cardiovascular outcomes despite intensive lipid lowering. The influence of inflammatory status on plaque-level morphological changes during PCSK9 inhibition remains incompletely understood.
Purpose
We evaluated intracoronary imaging changes following Evolocumab therapy stratified by residual inflammatory risk
Methods
This was a serial intravascular imaging sub-study of YELLOW III. Patients with stable CAD and lipid-rich, non-obstructive coronary plaques on maximally tolerated high-intensity statin therapy were treated with Evolocumab 140 mg every 2 weeks for 26 weeks. Serial multimodality intracoronary imaging of target non-obstructive lesions was performed at baseline and follow-up using OCT, IVUS, and NIRS. Lipid core burden index over 4 mm (LCBI4mm) was assessed by NIRS; fibrous cap thickness (FCT) by OCT; and total atheroma volume (TAV) and percent atheroma volume (PAV) by IVUS. Among 110 patients, 109 had hsCRP measurements. Baseline hsCRP values were available in 97 patients; in 12 patients without baseline hsCRP, follow-up values were used. Fifty-six of 109 patients (51.4%) had hsCRP ≥2 mg/L (RIR), and 53 (48.6%) had hsCRP <2 mg/L.
Results
When stratified by inflammatory status, baseline LCBI4mm did not differ significantly between patients with and without RIR (291.41 ± 186.61 vs. 321.91 ± 169.44; p = 0.375), nor did follow-up LCBI4mm (221.27 ± 188.13 vs. 199.57 ± 142.07; p = 0.500). The reduction in LCBI4mm demonstrated a trend toward attenuation in patients with residual inflammatory risk (ΔLCBI4mm −70.14 ± 123.65 vs. −122.34 ± 151.74; p = 0.051). Baseline FCT showed a trend toward lower values in the residual inflammatory risk group (67.32 ± 21.19 µm vs. 75.09 ± 21.63 µm; p = 0.061). However, follow-up FCT (94.11 ± 28.33 µm vs. 102.45 ± 33.05 µm; p = 0.159) and change in FCT (26.79 ± 21.50 µm vs. 27.36 ± 23.13 µm; p = 0.894) were not significantly different between groups. TAV did not differ at baseline (145.21 ± 85.21 vs. 128.85 ± 57.32; p = 0.245), at follow-up (140.42 ± 84.96 vs. 121.69 ± 54.56; p = 0.176), or in change over time (−4.79 ± 15.65 vs. −7.15 ± 7.97; p = 0.326). Similarly, PAV was comparable at baseline (51.28 ± 8.98 vs. 52.00 ± 9.04; p = 0.677), at follow-up (49.93 ± 8.74 vs. 50.56 ± 8.90; p = 0.709), and in change (−1.35 ± 1.38 vs. −1.44 ± 1.59; p = 0.753).
Conclusions
While Evolocumab therapy was associated with plaque stabilization characterized by fibrous cap thickening and lipid core reduction, inflammatory status did not significantly modify these effects. Trends toward lower baseline FCT and attenuated lipid core regression in patients with hsCRP ≥2 mg/L suggest that persistent inflammation may influence plaque phenotype and lipid remodeling despite intensive lipid lowering. Larger studies are warranted to further clarify the interaction between lipid lowering and inflammation at the plaque level.