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PCSK9-Inhibitoren

Aktuelle klinische Bedeutung

PCSK9 inhibitors

Current clinical relevance

  • Arzneimitteltherapie
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Zusammenfassung

Hintergrund

Hypercholesterinämien sind bekannte Risikofaktoren für kardiovaskuläre Erkrankungen. Obwohl Statine die kardiovaskuläre Morbidität und Mortalität gesenkt haben und weitere Therapieoptionen zur Verfügung stehen, werden die Therapieziele oft nicht erreicht. Bei sehr hohen Low-density-lipoprotein (LDL)-Cholesterin-Spiegeln und bei Unverträglichkeiten sind die etablierten Therapien oft nicht ausreichend effektiv oder können nicht in ausreichenden Dosen eingesetzt werden. Für diese Hochrisikopatienten werden zusätzliche Therapien benötigt.

Zielsetzung

Der Stellenwert der neuen Substanzklasse der proprotein convertase subtilisin/kexin type 9 (PCSK9)-Inhibitoren in der Therapie von Hypercholesterinämien wird auf Basis der aktuellen Datenlage und der deutschen Regularien dargestellt.

Datenlage

Zwei PCSK9-Inhibitoren, Evolocumab und Alirocumab, wurden 2015 zugelassen. Für beide Substanzen liegen Daten zu vielen verschiedenen Patientengruppen vor. Die signifikante Senkung von LDL-Cholesterin um 50–60 % und die sehr gute Verträglichkeit und Sicherheit auf Placeboniveau sind für beide PCSK9-Inhibitoren gezeigt. Nur bei der homozygoten familiären Hypercholesterinämie wirken sie nicht so effektiv. Die ersten Langzeitdaten und eine Bildgebungsstudie lassen erwarten, dass die Endpunktstudien die erwartete Senkung kardiovaskulärer Ereignisse zeigen werden. Langzeitstudien müssen die Sicherheit bestätigen. In Deutschland ist gesetzlich geregelt, bei welchen Patienten die PCSK9-Inhibitoren eingesetzt werden dürfen. Diese Vorgaben entsprechen weitgehend dem klinischen Vorgehen.

Schlussfolgerung

Die Datenlage wächst rasch, sodass die Grundlage für die Indikationsstellung immer besser wird. Die PCSK9-Inhibitoren werden unsere Möglichkeiten, Hochrisikopatienten optimal zu behandeln, deutlich verbessern.

Abstract

Background

Hypercholesterolemias are known risk factors for cardiovascular diseases. Although statins have reduced the cardiovascular morbidity and mortality and further therapeutic measures are available, treatment goals are often not achieved. In cases of very high levels of low-density lipoprotein (LDL) cholesterol or of intolerability, the established therapies are often not sufficiently effective or cannot be used in adequate doses. For these high-risk patients further treatment options are required.

Objectives

The current clinical relevance of the new substance class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for the treatment of hypercholesterolemias is presented on the basis of the available data and the German regulations.

Current data

The two PCSK9 inhibitors, evolocumab and alirocumab, were approved in 2015. Data from many different patient groups are available for both substances. The significant reduction of LDL cholesterol of 50–60% and the very good tolerability and safety profile (at placebo level) are shown for both substances. The PCSK9 inhibitors are not as effective only in homozygous familial hypercholesterolemia. The first long-term data and one imaging study raise hope that the endpoint trials will show the expected reduction in cardiovascular events. Long-term trials have to show the long-term safety. In Germany it is legally regulated which patients can be treated by PCSK9 inhibitors and these prerequisites are largely in accordance with clinical practice.

Conclusion

The body of evidence is rapidly increasing thereby facilitating the decision making when PCSK9 inhibitors could be used. The PCSK9 inhibitors will considerably improve the options for optimal treatment of high-risk patients.

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Authors and Affiliations

  1. Stoffwechselambulanz, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Ziemssenstr. 1, 80336, München, Deutschland

    A. Vogt

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Interessenkonflikt

A. Vogt hat Honorare oder Unterstützungen für Vorträge, Beratertätigkeiten, Studientätigkeiten oder Reisekosten erhalten, u. a. von: Aegerion, Amgen, D•A•CH-Gesellschaft Prävention von Herz-Kreislauf-Erkrankungen e. V., Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen DGFF (Lipid-Liga) e. V., Fresenius, Genzyme a Sanofi company, Kaneka, Merck Sharp & Dohme, Sanofi-Aventis.

Dieser Beitrag beinhaltet keine vom Autor durchgeführten Studien an Menschen oder Tieren.

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Vogt, A. PCSK9-Inhibitoren. Internist 58, 196–201 (2017). https://doi.org/10.1007/s00108-016-0179-7

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  • DOI: https://doi.org/10.1007/s00108-016-0179-7

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