Abstract
INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is a global health concern. Reducing low-density lipoprotein cholesterol (LDL-C) is critical in ASCVD prevention and treatment. Inclisiran, a novel RNA therapeutic agent, offers a promising solution by lowering LDL-C with twice-yearly dosing after an initial and 3-month dose. The study objective was to evaluate adherence to inclisiran and its lipid-lowering effectiveness over a year of treatment. METHODS: This retrospective cohort study involved patients over 18 years old with ASCVD or hyperlipidemia who initiated inclisiran between January 1, 2022, and May 17, 2023, in US outpatient clinics. LDL-C reduction was evaluated in patients with ≥ 1 pre- and post-index LDL-C measurement by comparing baseline levels to the lowest value within 12 months after initiating inclisiran. RESULTS: Overall, 225 patients initiated inclisiran. The mean age was 69.9 years and 50.7% were female. Most patients (81.8%) had ASCVD. Most patients (91.6%) received a second dose, and 84.5% of these received a third dose. Overall, 202 patients had ≥ 2 LDL-C measurements, with a mean baseline LDL-C of 134.8 mg/dl. Mean absolute LDL-C reduction was 66.1 (standard deviation: 45.6) mg/dl, corresponding to a 46.8% (95% confidence interval: 42.7-51.0) relative reduction, and 46.8% achieved ≥ 50% reduction. Patients on concurrent statins and those without prior anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibodies experienced the largest relative LDL-C reductions: 55.4% and 51.1%, respectively. CONCLUSIONS: Inclisiran significantly reduced LDL-C. The dosing schedule promoted high adherence in a real-world setting, particularly among older adults with ASCVD. These findings indicate inclisiran may be a particularly valuable addition to lipid-lowering strategies.