High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany
- PMID: 37422840
- PMCID: PMC10584696
- DOI: 10.1007/s00392-023-02247-8
High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany
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.
Keywords: Inclisiran; Low-density lipoprotein cholesterol; PCSK9; siRNA.
© 2023. The Author(s).
Conflict of interest statement
P.S., F.S. and G.J-A report no conflict of interest. U.M. reports speaker fee from the German Lipid Association, non-financial cooperation with Novartis and advisory board honoraria from Sanofi outside the submitted work. O.W. reports fees from Novartis, Daiichi Sankyo, Amgen, Sanofi, Fresenius, Novo Nordisk, Hexal, Akcea Therapeutics, Sobi and Pfizer outside the submitted work. W.K. reports consulting fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, DalCor, Kowa, Amgen, Corvidia, Daiichi-Sankyo, Genentech, Novo Nordisk, Esperion, OMEICOS, LIB Therapeutics, TenSixteen Bio, New Amsterdam Pharma, speaker honoraria from Amgen, Novartis, Berlin-Chemie, Sanofi, and Bristol-Myers Squibb, grants and non-financial support from Abbott, Roche Diagnostics, Beckmann, and Singulex outside the submitted work. T.W. reports research grants and/or speakers’ honoraria and/or advisory boards’ honoraria from Amgen, Daiichi-Sankyo, Novartis, and Sanofi Aventis outside the submitted work. U.L. reports fees from Novartis, Daiichi Sankyo, Amgen, Sanofi outside the submitted work. N.P reports advisory board honoraria from Bayer Vital GmbH and speaker honoraria from Novo Nordisk, CardioMetabolic Health Conference and The Metabolic Institute of America, GWT outside the submitted work. A.V. reports fees from Amgen, Daiichi Sankyo, Novartis, Regeneron/Sanofi outside the submitted work. D.S. reports speaker and advisory board honoraria from Amgen, Novartis, and Daiichi-Sankyo, consulting fees from Sanofi, and participation in clinical trials with Novartis, outside the submitted work. E.S-T. reports fees for lectures and/or advisory board honoraria from Fresenius Medical Care. Daiichi-Sankyo, Novartis, Amgen, Amarin, Sanofi, Pfizer outside the submitted work. U.S. reports speaker and advisor honoraria from Amgen, Amarin, Astra Zeneca, Berlin Chemie, Daiichi Sankyo, Lilly, Novartis, NovoNordisk, Sanofi Aventis outside the submitted work. U.K. reports fees from Amgen, Daiichi Sankyo, Novartis, Regeneron/Sanofi outside the submitted work. I. E. reports speaker honoraria from Novartis, Daiichi-Sankyo, Sanofi, Bristol-Myers Squibb, Bayer, Boehringer-Ingelheim and Astra Zeneca outside the submitted work. E.L. reports speaker fees from AMGEN, Novartis and Sanofi outside the submitted work.
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