Real-world efficacy of inclisiran: data from a tertiary lipid clinic

Small-interfering RNA (siRNA)-based therapies, such as inclisiran, offer a novel approach to reducing low-density lipoprotein-cholesterol (LDL-C) and preventing cardiovascular disease (CVD). Inclisiran inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis, enhancing LDL-receptor recycling and LDL-particle clearance. Although clinical trials have established its efficacy with LDL-C reductions of 44-52%, real-world studies have reported variable reductions over shorter follow-up periods. This study aimed to assess the long-term efficacy and safety of inclisiran in a diverse real-world cohort. A total of 238 patients initiating inclisiran between January 2022 and January 2024 at a tertiary lipid service were included. Data on lipid profiles, comorbidities, and medication history were collected from electronic healthcare records. LDL-C reductions were analysed at each dose using a Bayesian hierarchical model, and subgroup analyses explored the influence of familial hypercholesterolaemia (FH) and baseline lipid-lowering therapy. Inclisiran therapy resulted in a mean LDL-C reduction of 48.4% following the first dose, sustained over 27 months. Patients receiving three or more lipid-lowering therapies at baseline achieved greater LDL-C reductions compared with others (67.4% after first dose vs. 47.6%). No discernible differences in efficacy were observed between patients with and without FH. Inclisiran was well tolerated, with only six patients discontinuing therapy due to adverse events or preference. Approximately 35% of patients met the European Society of Cardiology LDL-C target of <1.4 mmol/L after the first dose, declining to 28% after the fourth dose. These real-world findings demonstrate that inclisiran is a well-tolerated and effective lipid-lowering therapy, achieving reductions comparable with clinical trial results. Greater reductions in patients on multiple baseline therapies suggest the importance of comprehensive lipid management. While achieving stringent LDL-C targets remains challenging, inclisiran's practical benefits, including infrequent dosing and good tolerability, underscore its potential to improve CVD outcomes in diverse populations.