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.
Hadzhiveli et al. (Mon,) studied this question.