LDL-C reduction with inclisiran in real-world clinical practice: an observational study

Abstract Background Atherosclerotic cardiovascular diseases (ASCVD)remain the leading cause of morbidity and mortality globally.Low-density lipoprotein cholesterol (LDL-C is a major risk factor for them,which necessitate stringent control.Despite maximized conventional lipid-lowering therapies (LLT),a significant proportion of high-risk patients fail to reach guideline-recommended LDL-C goals.Data regarding the real-world effectiveness and safety of inclisiran in clinicalpractice settings,particularly within Eastern European populations, remain scarce. Aim to evaluate the efficacy and safety profile of inclisiran in reducing low-density lipoprotein cholesterol (LDL-C)levels and achieving target goals among patients with familial hypecholesterolemia (FH)with or without established ASCVD. Methods A retrospective,observational study of anonymous clinical data collected from electronic health records of patients treated in multiple medical centres across Eastern Bulgaria. Patients above 18 years with DLCN criteria of FH≥6 who initiated inclisiran between January 2023 and August 2025 were included. A total of n=100 patients were included in the final analysis. All patients received the standard Inclisiran dosing regimen (initial dose, followed by a second dose at 3 months, and subsequent doses every 6 months).The primary efficacy endpoint was the mean percent change inLDL-C from baseline to 12 months post-initial dose. Secondary endpoints included the proportion of patients achieving guideline-recommended LDL-Ctargets (based on the 2019 ESC/EAS guidelines). Primary safety endpoint was the assessment of treatment-emergent adverse events over the follow-up period. Statistical analyses descriptive statistics and paired t-tests to compare lipid values, with P0.05 considered statistically significant. Results The mean age was 56.3±9.10 (SD)years and 68.6 % were males. Efficacy (n=42): The mean baseline LDL-C level was 4.48±1.79(SD) mmol/L.After Inclisiran treatment the mean percent change in LDL-C was-65. 1±17.5 (SD)%(P0.001)At 12 months, 63.8% of patients achieved the guideline-recommended LDL-C target 1.4 mmol/L for ASCVD/ very high risk, and 1,8 for high risk/ No ASCVD)- ASCVD/Very High Risk (n=40) 65% and Non-ASCVD (n=7): 57 %. Safety (n=100): Safety analysis revealed a favourable tolerability profile. No treatment-related serious adverse events (SAEs) or drug-related withdrawals were documented throughout the follow-up period. Minor adverse events (e.g.,injection site reactions) were not systematically reported in the electronic health records and thus could not be accurately quantified. Conclusion In this real-world, observational study, Inclisiran achieved a substantial and sustained reduction in LDL-C. The majority of the patients successfully reached the recommended ESC/EAS LDL-C goals, with no significant adverse reactions. These findings strongly support the implementation of Inclisiran in routine clinical practice for secondary and primary prevention of ASCVD in FH.