Key result
Inclisiran cuts LDL-C by ~28% in real-world practice, though discontinuation reaches ~28%.
Why the study?
Real-world evidence on the long-term effectiveness and treatment persistence of inclisiran remains limited.
What are the long-term LDL-C reductions, treatment persistence, and reasons for therapy discontinuation with inclisiran over up to 3 years of follow-up in a real-world lipid clinic cohort?
Cohort (n=109)
Yes
What are the long-term LDL-C reductions, treatment persistence, and reasons for therapy discontinuation with inclisiran over up to 3 years of follow-up in a real-world lipid clinic cohort?
Answers are grounded in this paper and cite their sources.
In a 3-year real-world German cohort, inclisiran was well tolerated by statin-intolerant patients (86.7% adverse-event free) and yielded a 46% nadir LDL-C reduction, but showed a modest 28% median LDL-C reduction across visits with high intra-/interindividual variability and a 28.4% discontinuation rate.
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.
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Makhmudova et al. (2026) conducted a cohort in Dyslipidemia / Elevated LDL-C failing to achieve EAS/ESC guideline target levels (n=109). Inclisiran therapy was evaluated on Median LDL-C percentage reduction from baseline across follow-up timepoints (Median LDL-C change -28.0%, 95% CI -33.8 to -24.2, p=<0.001). Inclisiran reduced LDL-C by a median of 28.0% (95% CI -33.8 to -24.2%) over 33 months in real-world practice, though 28.4% of patients discontinued therapy.
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