# High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany

Article · Makhmudova U, Schatz U, Perakakis N, Kassner U, Schumann F, Axthelm C, Stürzebecher P, Sinning DL, Doevelaar A, Rohn B, Westhoff T, Vogt A, Scholl M, Kästner U, Geiling JA, Stach K, Mensch J, Lorenz E, Paitazoglou C, Eitel I, Baessler A, Steinhagen-Thiessen E, Koenig W, Schulze PC, Landmesser U and 2 more

- Archive id: doi:10.1007/s00392-023-02247-8
- Published: 2023-07-09
- Venue: Clinical research in cardiology : official journal of the German Cardiac Society
- DOI: https://doi.org/10.1007/s00392-023-02247-8
- PMID: 37422840
- PMCID: PMC10584696
- Citations: 43
- Source URL: https://doi.org/10.1007/s00392-023-02247-8
- PDF: https://europepmc.org/articles/PMC10584696/pdf
- Provenance: europepmc

## Abstract

Background and aims Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. Methods Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. Results Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). Conclusion In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cardiovascular Therapeutics](https://space-kitty.com/topics/cardiovascular-innovation)

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