Serial Coronary Plaque Composition After Inclisiran Initiation Assessed by Automated CCTA: A Retrospective Pilot Study.

Background/Objectives: Inclisiran provides durable low-density lipoprotein cholesterol (LDL-C) lowering, but serial coronary plaque composition after treatment initiation remains incompletely characterized. This study evaluated temporal plaque changes using automated coronary computed tomography angiography (CCTA). Methods: In this uncontrolled, retrospective, observational pilot study, consecutive patients who initiated inclisiran between 1 January 2024 and 29 April 2026 were screened. A random-intercept mixed-effects model included every eligible quantitative plaque observation obtained by the prespecified data cutoff. Results: Of the 230 screened patients, 215 contributed 468 plaque observations (baseline, n = 186; 3 months, n = 196; 15 months, n = 86); 74 had all three examinations. The LDL-C levels decreased from 117.4 mg/dL (95% confidence interval [CI], 113.3-121.6) to 45.9 mg/dL (39.5-52.3) at 15 months. No significant time effect was detected for the total plaque volume (p = 0.713). Low-density non-calcified plaque (LDNC) decreased from 27.3 mm3 (23.1-31.6) to 22.7 mm3 (18.0-27.4; overall p = 0.0035), whereas calcified plaque increased from 56.5 mm3 (45.6-67.3) to 67.1 mm3 (55.9-78.2; p < 0.0001). The adjusted baseline-to-15-month differences were -4.64 mm3 for LDNC (95% CI, -7.54 to -1.74; Bonferroni-adjusted p = 0.0052) and +10.60 mm3 for calcified plaque (6.60-14.60; adjusted p < 0.0001). In the tube voltage-adjusted sensitivity analysis of 107 patients and 278 observations, these findings were maintained. Conclusions: Patients initiating inclisiran showed temporal changes in attenuation-defined plaque composition. The uncontrolled design, incomplete acquisition data in the expanded cohort, and technical variability preclude causal or histologic interpretation.