Real-World Efficacy of Inclisiran in Veneto Region (Italy): The INCLIVEN Multicenter Registry.

Abstract

Purpose: Inclisiran is a long-acting small interfering RNA (siRNA) which prevents the synthesis of PCSK9 in hepatocytes, reducing LDL-C concentration. Only limited data are available in the literature regarding its use in real-world settings.

Methods: In this observational multicenter registry, we included high cardiovascular risk patients from 12 lipid clinics in the Veneto region of Italy who started inclisiran therapy between October 2022 and February 2024. Primary endpoint was changes in LDL-C concentrations at 3 months of follow-up after inclisiran administration. Secondary endpoints were changes in LDL-C concentrations at 9 months of follow-up, safety, percentage of patients reaching LDL-C targets and efficacy of inclisiran according to background therapy and clinical characteristics of the population.

Results: Mean LDL-C levels at baseline (n = 240) were 118.7 ± 48.7 mg/dl, then they significantly fell to 56.7 ± 40.4 mg/dl (-52.3 ± 24.3%; p < 0.001) at 3 months (n = 238) and to 60.5 ± 40.1 mg/dl (-50.0 ± 22.7%; p < 0.001) at 9 months (n = 138). Three (1.3%) patients reported mild injection-site side effects. LDL-C target achievement according to ESC/EAS 2019 guidelines was 64.7% at 3 months and 62.3% at 9 months. Patients on statin therapy had a greater LDL-C reduction compared to patients with statin intolerance. At 3 months across we observed greater LDL-C reduction in patients with diabetes (59.9 ± 23.2% vs 49.7 ± 24.1%; p = 0.004). In the multivariable analysis diabetes mellitus (p = 0.006) and background statin therapy (p = 0.034) were independent predictors for greater LDL-C reduction.

Conclusion: This real-world multicenter registry supports inclisiran as an effective, well-tolerated option for managing hypercholesterolemia in high cardiovascular risk patients.