{"id":"doi:10.1007/s00392-023-02247-8","kind":"article","title":"High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany","authors":["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"],"author_count":27,"year":2023,"published":"2023-07-09","venue":"Clinical research in cardiology : official journal of the German Cardiac Society","cited_by":43,"doi":"10.1007/s00392-023-02247-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1007/s00392-023-02247-8","archive_url":"https://space-kitty.com/papers/doi:10.1007/s00392-023-02247-8","updated":null,"pmid":"37422840","pmcid":"PMC10584696","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10584696/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany\" by Makhmudova U, Schatz U, Perakakis N et al., https://doi.org/10.1007/s00392-023-02247-8, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cardiovascular-innovation","name":"Cardiovascular Therapeutics","domain_slug":"medicine"}],"cited_in_dossiers":[]}