Long-term LDL-C lowering and treatment persistence with inclisiran: 3-year follow-up from the German Inclisiran Network

Abstract Background Inclisiran, a small interfering RNA targeting PCSK9, has demonstrated durable LDL-C lowering in clinical trials. However, real-world evidence on its long-term effectiveness and treatment persistence remains limited. Aim To evaluate LDL-C reductions, treatment persistence, and reasons for therapy discontinuation over a follow-up period of up to 3 years in a real-world lipid clinic cohort. Methods We analyzed data from ten lipid clinics participating in the German Inclisiran Network (GIN). Adults with at least one inclisiran dose and follow-up lipid measurements were included. LDL-C levels were assessed during 3 years of follow-up (median 33 months, IQR 27–39). Discontinuation rates, therapy changes, and adverse effects were documented. Results Among 109 patients (mean age 63.8 years, 43.1% female). The cohort comprised a heterogeneous population, with only ~ 30% receiving statins due to statin intolerance. Median (95% CI) LDL-C reduction from baseline to nadir was − 46% (− 60.8 to − 33.8%). Median for LDL-C reduction for each individual during the follow-up was − 28% (− 33.8 to − 24.2%). High interindividual and intraindividual variability in LDL-C response was observed. Over 3 years, ~ 30% of patients discontinued inclisiran, most commonly due to lack of efficacy (15.6%), adverse effects (7.3%), or a combination of both (1.8%). Those who discontinued due to lack of efficacy were older and had less background lipid-lowering therapy. Females were more likely than males to discontinue due to adverse effects. In a multivariable logistic regression model, older age was a predictor of higher discontinuation rates, whereas concomitant LLT use was associated with lower discontinuation rates. Notably, ~ 87% of patients with statin intolerance did not exhibit any adverse effects with inclisiran. Conclusions In a heterogeneous real-world population, inclisiran achieved significant LDL-C reductions but with marked inter- and intraindividual variability. A notable proportion of patients discontinued therapy, highlighting the importance of individualized treatment strategies.