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Publications

Journal Article Ahead of print

PubMed: 42803952 DOI: 10.1007/s00392-026-03028-9

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

Clin Res Cardiol

Authors: Umidakhon Makhmudova, Ulrike Schatz, Paulina Stuerzebecher, Friederike Schumann, Uta Kästner, Juliane Mensch, Jens Arndt Geiling, Franz Haertel, Ksenija Stach, Anja Vogt, Andrea Bässler, David Sinning, Ursula Kassner, Elisabeth Steinhagen-Thiessen, P Christian Schulze, Ulf Landmesser, Ulrich Laufs, Oliver Weingärtner

Affiliations

  • Friede Springer Cardiovascular Prevention Center at Charité, Charité Universitätsmedizin Berlin, Berlin, Germany.
  • Deutsches Herzzentrum Der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Berlin, Germany.
  • Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
  • Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany.
  • Department of Cardiology, University Hospital Leipzig, Leipzig, Germany.
  • Clinic for Endocrinology and Metabolic Medicine, Charité , Berlin, Germany. Institute for Clinical Chemistry, University Medicine Rostock, Rostock, Germany.
  • Medical Care Centre, Nephrocare Mühlhausen GmbH, Mühlhausen/Thuringia, Germany.
  • Institute for Clinical Chemistry, University Medicine Rostock, Rostock, Germany.
  • Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, Friedrich- Schiller-University, University Hospital Jena, 07747, Jena, Germany.
  • Department of Internal Medicine V, University Hospital Mannheim, Mannheim, Germany.
  • Department of Internal Medicine IV, University Hospital Munich, Munich, Germany.
  • Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
  • Deutsches Herzzentrum Der Charité, Department of Cardiology, Angiology and Intensive Care Medicine, Berlin, Germany. Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany. ATOS MVZ KANT KARDIO, Berlin, Germany.
  • Clinic for Endocrinology and Metabolic Medicine, Charité , Berlin, Germany.
  • Department of Internal Medicine I, Division of Cardiology, Angiology and Intensive Medical Care, Friedrich- Schiller-University, University Hospital Jena, 07747, Jena, Germany.

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.

MeSH

Heart Diseases, Therapeutics, Hydroxymethylglutaryl-Coa Reductase Inhibitors