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Lipidsenkung: neue Substanzen und neue Konzepte

Lipid lowering: new agents and new concepts

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Zusammenfassung

LDL(„low-density lipoprotein“)-Cholesterin (LDL-C) ist ein kausaler Risikofaktor für kardiovaskuläre Komplikationen. Ein Zielwert wird risikobezogen, leitlinienbasiert und individualisiert festgelegt. Wir haben heutzutage die Möglichkeiten, LDL-C-Werte in Bereiche zu senken, die sogar mit einer Regression des Plaquevolumens verbunden sind. Zudem ist die Lipidtherapie ein Beispiel, wie sich die Pharmakotherapie von klassischen selektiven Hemmungen von Enzymen durch Medikamente (z. B. Statine) zur gezielten Neutralisierung von Proteinen durch Antikörper entwickelt hat. Die Reduktion atherogener Lipoproteine durch spezifische Hemmung oder Verminderung der mRNA von Zielproteinen (z. B. PCSK9, ANGPLT3, ApoC-III oder Apolipoprotein[a]) sowie eventuell eines Tages durch Impfung oder auch CRISP-basierte Gentherapie wird langfristig zu neuen Konzepten in der Therapie und Prävention von Fettstoffwechselstörungen und kardiovaskulären Komplikationen führen. Die kumulative Exposition atherogener Lipoproteine für die Gefäßwand wird durch den zeitlich gemittelten LDL-C-Wert bestimmt. Dieser hängt wesentlich von der Adhärenz des Patienten und der verordneten Behandlungsintensität durch Ärzte ab. Daher ist es wahrscheinlich, dass die Therapietreue den kumulativen Nutzen der Therapie beeinflusst. Entsprechend könnten die neuen, o. a. Therapiestrategien mit vermutlich höheren Adhärenzraten dazu beitragen, die kardiovaskuläre Prävention zu optimieren. Eine frühzeitige und effektive LDL-C-Senkung könnte langfristig das Auftreten kardiovaskulärer Komplikationen drastisch reduzieren und dazu beitragen, die Gesundheit unserer Patienten zu erhalten.

Abstract

Low-density lipoprotein (LDL) cholesterol (LDL-C) is a causal risk factor for cardiovascular complications. A target value is set according to risk, guideline-based and individual basis. We now have the means to lower LDL‑C levels to ranges that are even associated with plaque volume regression. Moreover, lipid treatment is an example of how pharmacotherapy has evolved from classical selective inhibition of enzymes by drugs (e.g. statins) to targeted neutralization of proteins by antibodies. The reduction of atherogenic lipoproteins by specific inhibition or reduction of mRNA of target proteins, e.g. PCSK‑9, ANGPLT3, ApoC-III or Apo (a), and possibly one day by vaccination or even CRISP-based gene therapy will in the long term lead to new concepts in the treatment and prevention of dyslipidemia and cardiovascular complications. The cumulative exposure of atherogenic lipoproteins to the vessel wall is determined by the time-averaged LDL‑C level. This essentially depends on patient adherence and prescribed treatment intensity by physicians. Therefore, it is likely that treatment adherence influences the cumulative benefit of treatment. Accordingly, the new therapeutic strategies mentioned above with presumably higher adherence rates could help to optimize cardiovascular prevention. Early and effective LDL‑C lowering could drastically reduce the incidence of cardiovascular complications in the long term and help to maintain the health of our patients.

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  1. Medizinische Klinik I, Universitätsklinikum RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland

    Julia Brandts, Marlo Verket &  Dirk Müller-Wieland

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Correspondence to Dirk Müller-Wieland.

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Interessenkonflikt

J. Brandts hat Honarare für Beratung und Vorträge erhalten von Amgen und AstraZeneca. D. Müller-Wieland hat Honorare für Beratung und Vorträge erhalten von Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Lilly, Merck Sharp & Dohme, Novo Nordisk und Sanofi. M. Verket gibt an, dass kein Interessenkonflikt besteht. Forschungsförderung geht projektbezogen an das klinische Studienzentrum der Klinik bzw. des UKA.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Brandts, J., Verket, M. & Müller-Wieland, D. Lipidsenkung: neue Substanzen und neue Konzepte. Herz 47, 419–425 (2022). https://doi.org/10.1007/s00059-022-05133-7

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