Long term efficacy and adherence of inclisiran in real-world clinical practice: insights from the CHOLINET Registry

Background/Introduction Inclisiran has proven to be effective in lowering low-density lipoprotein cholesterol (LDL-C) in randomized clinical trials and real-world settings. However, long-term data on efficacy and adherence of inclisiran in real-world clinical practice are limited. Purpose CHOLINET (Cholesterol inclisiran Italian network) is an Italian multicenter observational registry on the use of inclisiran in clinical practice. The purpose of this analysis was to evaluate long term efficacy and adherence of inclisiran in a real-world setting. Methods The CHOLINET registry enrolled patients receiving inclisiran according to standard clinical practice and national reimbursement criteria. Clinical and demographic characteristics, concomitant therapies, and blood chemistry were recorded at the time of first prescription and at subsequent follow-ups. Efficacy endpoints included LDL-C reduction and achievement of guideline-recommended LDL-C targets at 3, 9, 15, and 21 months. Results A total of 1428 patients were enrolled between November 2022 and February 2026. Mean age was 62.6±10.6 years, and the majority were male (67.2%). Baseline median LDL-C was 109 mg/dL (Q1-Q3: 81-156 mg/dL). Of these patients, 1090 reached the 3-month follow-up (FU), 682 the 9-month FU, 367 the 15-month FU, and 199 reached the 21-month follow-up at the time of this analysis. Median LDL-C reduction was 48.9% (Q1-Q3: 30.8-66) at 3 months, 51.8% (32.5-66.9) at 9 months, 51.2% (34.4-63.9) at 15 months, and 48,0% (24-64.6) at 21 months. Furthermore, 51.6% of patients reached LDL-C targets at 3 months, 53.2% at 9 months, 50.4% at 15 months, and 48.2% at 21 months. Patients receiving statin±ezetimibe showed greater LDL-C reduction compared to those not on combination therapy at 3 (57.3% vs 38.2%; p<0.001), 9 (58.5% vs 42.9%; p<0.001), and 15 (54.3% vs 46.7%; p<0.001) months. Similarly, target attainment was significantly higher in patients receiving statin±ezetimibe, at any time point at 3 (67.2% vs 26.1%; p<0.001), 9 (71.7% vs 26.4%; p<0.001), and 15 (67.1% vs 26.5%; p<0.001) months. Overall, 46 patients (3.2%) discontinued inclisiran. Adherence was 97.9% at 3 months, 97.8% at 9 months, 98.1% at 15 months, and 99.5% at 21 months. Conclusion(s) In real-world practice, inclisiran shows sustained LDL-C reduction up to 21 months, with approximately 50% target attainment and low discontinuation rates. Background statin ± ezetimibe therapy improves both LDL-C lowering and target achievement.