关键词: 急性冠脉综合征, 英克司兰, PCSK9单克隆抗体, 低密度脂蛋白胆固醇, LDL-C变异性, 累积暴露量, 真实世界研究

Abstract:

Objective This study aims to assess the lipid-lowering efficacy of Inclisiran and proprotein convertase subtilisin/kexin type 9 （PCSK9） monoclonal antibodies （PCSK9mAbs） in patients with Acute Coronary Syndrome （ACS） by utilizing real-world clinical data. Methods This study adopted a single-center retrospective cohort design， enrolling patients with ACS who were treated with Inclisiran or PCSK9 monoclonal antibodies （mAbs， including evolocumab and alirocumab） at the Cardiology Department of Tianjin Chest Hospital from January 2022 to March 2024. All enrolled patients were those who failed to reach the low-density lipoprotein cholesterol （LDL-C） targets after at least 30 days of stable moderate-intensity statin therapy. By using propensity score matching at a 1∶2 ratio， the patients were divided into an Inclisiran group （n = 31） and a PCSK9 monoclonal antibody group （n = 55）. Lipid profiles were collected and analyzed at the start of treatment and during three follow-up visits （1 ~ 3 months， 3 ~ 9 months， and 9 ~ 12 months after discharge）. The differences between the two groups were compared in terms of the percentage reduction of LDL-C from the baseline， the LDL-C target achievement rates， the trend of LDL-C changes， and the cumulative LDL-C exposure during the follow-up period. The differences in LDL-C variability between the two groups were evaluated by the standard deviation （SD） and the average successive variability （ASV）. Results The LDL-C reduction in the Inclisiran group was significantly superior to that in the PCSK9 mAbs group at all three follow-up visits （P < 0.05）. In terms of the attainment rate， the Inclisiran group demonstrated a higher LDL-C target attainment rate than the PCSK9 monoclonal antibody group at each visit （P < 0.05）， and up to 80.65% of patients achieved sustained attainment （with a target value of 1.8 mmol/L）. After adjusting for baseline LDL-C levels， the Inclisiran group showed a more substantial reduction in LDL-C than the PCSK9 monoclonal antibody group （β = -0.300， 95%CI： -0.535 to -0.064， P = 0.013）. The trends of LDL-C changes over time were similar between the two groups. Moreover， the Inclisiran group had lower lipid variability （between-group P for SD = 0.034； between-group P for ASV = 0.029） and lower cumulative LDL-C exposure （P < 0.01） compared to the PCSK9 monoclonal antibody group. Conclusion In statin-treated ACS patients， inclisiran demonstrated superiority over PCSK9 monoclonal antibodies （mAbs） in reducing LDL-C levels， enhancing target achievement rates， decreasing cumulative LDL-C exposure， and maintaining LDL-C stability.

Key words: acute coronary syndrome, inclisiran, PCSK9 monoclonal antibodies, low-density lipoprotein cholesterol, LDL-C variability, cumulative exposure, real-world study