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HDL – „Game over“?

HDL – Game over?

  • Klinische Pharmakologie
  • Published:
Der Kardiologe Aims and scope

Zusammenfassung

Das Verfehlen primärer Endpunkte in mehreren aktuellen Studien zur Wirksamkeit High-density-Lipoprotein (HDL)-Cholesterin erhöhender Therapien begründet zusammen mit neuen Ergebnissen der genetischen Epidemiologie Zweifel an HDL als therapeutischem Ziel. Sowohl die vorliegenden Cholesteryl-Ester-Transfer-Protein (CETP)-Hemmer-Outcome-Studien mit Torcetrapib und Dalcetrapib sowie die Daten zu Niacin zuerst in der AIM-HIGH-Studie und aktuell im erheblich größeren HPS2-THRIVE-Trial klären jedoch nicht abschließend, ob HDL ein falsches Behandlungsziel ist. Klinisch relevante Perspektiven liegen in Erfassung und therapeutischer Beeinflussung der HDL-Funktionalität, für die HDL-Cholesterin kein ausreichendes Maß ist. Als Marker des kardiovaskulären Risikos und hiermit Bestandteil der Entscheidung des therapeutischen Low-density-Lipoprotein (LDL)-Cholesterin-Ziels behält HDL-Cholesterin Bedeutung. Die laufenden Studien mit weiteren CETP-Hemmern werden zur Beantwortung der Fragestellung von HDL als therapeutischem Ziel beitragen.

Abstract

The failure of recent clinical trials to improve cardiovascular outcome via pharmacological high density lipoprotein (HDL) cholesterol manipulation and findings that genetically increased concentrations of HDL cholesterol in plasma do not lower the risk of myocardial infarction may question the usefulness of HDL cholesterol as a measure in clinical practice. Cholesteryl ester transfer protein (CETP) inhibition was shown to raise HDL cholesterol levels but the CETP inhibitors torcetrapib and dalcetrapib have shown no clinical benefit. The broad spectrum of lipid-modifying activity of niacin, including HDL cholesterol (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides and lipoprotein (a) did not translate into improved clinical outcome in the AIM-HIGH trial and the HPS2-THRIVE trial. New pharmacological data contribute to explanations why evaluating the effects of the combination of extended release (EC) niacin with the prostaglandin D(2) receptor antagonist laropiprant in the HPS2-THRIVE trial showed no improvement in cardiovascular outcome. That HDL cholesterol is a poor metric for targeted intervention and methodological issues of the trials are parts of the current controversy. It has been established that HDL is heterogeneous and contains particles with different lipid compositions and separate anti-atherosclerotic functions. Low HDL due to genetic mutations in apoA-I, the structural protein of HDL, can be causative in syndromes with premature atherosclerosis. It is known that HDL cholesterol has a role as a marker of a high risk for dyslipoproteinemia; however, HDL function may be a preferable measure in the future. Data from ongoing outcome studies with the newer CETP inhibitors anacetrapib and evacetrapib will be crucial for the future of HDL as an important approach to decreasing cardiovascular morbidity and mortality.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. G. Klose: Vortragshonorare, Symposiumsunterstützung oder Advisory-Board-Tätigkeiten bei Amgen, BMS, Genzyme, MSD, Roche, Sanofi. R. Hambrecht: Astra, Pohl-Boskamp, Berlin Chemie – Vortragstätigkeiten; MSD, Fa. Lilly – Beratertätigkeiten. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Praxis Dres T. Beckenbauer & S. Maierhof, Am Markt 11, 28195, Bremen, Deutschland

    G. Klose

  2. Bremer Institut für Herz- und Kreislaufforschung, Klinikum Links der Weser, Bremen, Deutschland

    R. Hambrecht

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  1. G. Klose
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  2. R. Hambrecht
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Correspondence to G. Klose.

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Klose, G., Hambrecht, R. HDL – „Game over“?. Kardiologe 7, 346–351 (2013). https://doi.org/10.1007/s12181-013-0505-4

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  • DOI: https://doi.org/10.1007/s12181-013-0505-4

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