OBJECTIVE: To gain an improved comprehension of inclisiran safety in real-world settings by data mining from the US Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). METHODS: In a retrospective pharmacovigilance study, disproportionality analysis was utilized to determine the AEs associated with inclisiran use as signals. Data were gathered between 1 December 2020 and 31 December 2023. The Medical Dictionary for Regulatory Activities (MedDRA) corresponding preferred term (PT) and system organ class (SOC) were used to categorize adverse medication reactions in AE reports (AERs). By using reported odds ratio (ROR) method, positive signals were identified. Clinical prioritization of signals was ranked by a semiquantitative score method based on three categories of clinical significance. This was performed by assessing five distinct features: AER number, ROR value, mortality percentage, designated (DME) or important medical event (IME), and biological plausibility. RESULTS: There were 2,652 reports of inclisiran, and 150 of those AEs had significant disproportionality signal. The clinical priority scores elucidated that 106 (70.67%), 44 (29.33%), and 0 PTs were classified as weak, moderate, and strong clinical priorities, respectively. Among the 44 PTs with moderate clinical priority, 35 PTs were discovered on the medicine label, including 12 IMEs and 2 DMEs, such as pancreatitis (DME, ROR 3.29), deafness (DME, ROR 2.10), myocardial Infarction (IME, ROR 3.50), angina unstable (IME, ROR 17.11), coronary artery occlusion (IME, ROR 5.65), arrhythmia (IME, ROR 2.15). Of note, 9 PTs had unanticipated AEs that were discovered in the medication label or reported clinical studies, such as movement disorder (ROR: 3.05
95%CI: 1.73,5.37), aphonia (ROR: 3.77
95%CI: 1.79,7.91), and pulmonary congestion (ROR: 3.47
95%CI: 1.44,8.34). Inclisiran was found to be related to 12 serious AEs, including gait disturbance, hypertension, arthralgia, urinary tract infection, diabetes mellitus, dizziness, myocardial infarction, and chest pain. The median TTO of 1896 cases was 13.5 (IQR 0-100) days. Additionally, 39.72% (753/1896) of AEs occurred during the first day post-inclisiran commencement. CONCLUSION: We identified not only known AEs, but also new AE signals such as movement disorder.However, signals does not reveal actual risk, prospective clinical trials are still required to verify their causal connection.