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Kardiovaskuläre Risikopatienten unter Androgenentzugstherapie

Geringeres Risiko mit GnRH-Antagonisten im Vergleich zu LHRH-Agonisten?

Cardiovascular risk patients under androgen deprivation therapy

Lower risk with GnRH antagonists compared to LHRH agonists?

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Zusammenfassung

Hintergrund

Die Androgendeprivationstherapie (ADT) ist die tragende Säule der Behandlung des metastasierten Prostatakarzinoms (mPCa), wird aber auch mit dem Auftreten kardiovaskulärer Ereignisse in Verbindung gebracht. Bisher existieren nur wenige Studien, die LHRH-Agonisten und GnRH-Antagonisten in Bezug auf das kardiovaskuläre Risiko direkt miteinander vergleichen.

Ziel der Arbeit

Dieser Artikel vergleicht das kardiovaskuläre Risiko von LHRH-Agonisten und GnRH-Antagonisten basierend auf der aktuellen Fachliteratur.

Methoden

Eine Literaturrecherche wurde durchgeführt, in der Vollpublikationen und Abstracts, die bis zum 10. Dezember 2014 erschienen, berücksichtigt wurden. Evidenzbedingt wurde die Literaturrecherche auf Metaanalysen und gepoolte Studiendaten beschränkt.

Ergebnisse

Vier Arbeiten untersuchten das kardiovaskuläre Risiko unter einer Therapie mit LHRH-Agonisten und/oder GnRH-Antagonisten, aber nur eine Arbeit stellte einen direkten Vergleich des kardiovaskulären Risikos unter LHRH-Agonisten und GnRH-Antagonisten an. Aus dieser Metaanalyse ergibt sich ein signifikant geringeres Risiko für Patienten unter einem GnRH-Antagonisten im Vergleich zu einem LHRH-Agonisten (HR: 0,597; 95 % CI: 0,380–0,938; p = 0,0253). Subgruppenanalysen zeigen, dass vor allem Patienten mit kardiovaskulärer Vorerkrankung ein deutlich vermindertes Risiko für das Auftreten eines kardiovaskulären Ereignisses haben, wenn sie mit GnRH-Antagonisten und nicht mit LHRH-Agonisten behandelt werden (HR: 0,44; 95 % CI: 0,26–0,74; p = 0,002).

Schlussfolgerungen

Das Risiko für ein kardiovaskuläres Ereignis unter ADT mit GnRH-Antagonisten ist im Vergleich zu LHRH-Agonisten, insbesondere für PCa-Patienten mit kardiovaskulären Vorerkrankungen, geringer. Daher empfehlen wir, diese Patienten mit GnRH-Antagonisten zu behandeln.

Abstract

Background

Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonists is the mainstay of treatment for metastatic prostate cancer (mCaP). However, ADT is associated with serious cardiovascular events. Only a few studies that directly compare the cardiovascular risk of LHRH agonists versus GnRH antagonists have been published.

Objectives

This review aims to compare the cardiovascular risk of LHRH agonists versus GnRH antagonists based on the literature.

Methods

A literature search that considered full publications and abstracts published before December 10, 2014 was performed. Due to their high evidence quality, only meta-analyses and pooled studies were included in this review.

Results

Four studies were included. These investigated the cardiovascular risk of patients receiving an ADT with LHRH agonists and/or GnRH antagonists. However, only one of these directly compared the cardiovascular risk of ADT with LHRH agonists versus GnRH antagonists. This meta-analysis showed a significant reduction in cardiovascular risk for patients receiving a GnRH antagonist compared to those patients receiving a LHRH agonist (HR: 0.597; 95 % CI: 0.380–0.938; P = 0.0253). Subgroup analyses showed that, in particular, patients with pre-existing cardiovascular diseases who were treated with a GnRH antagonist have a significantly lower risk of experiencing a cardiovascular event when compared with patients receiving a GnRH agonist (HR: 0.44; 95 % CI: 0.26–0.74; P = 0.002).

Conclusion

In conclusion, GnRH antagonists are associated with a lower risk of cardiovascular events, compared with LHRH agonists, when administered as ADT in CaP patients, and particularly in patients with a history of cardiovascular disease. Thus, patients with a history of cardiovascular disease may benefit from ADT with a GnRH antagonist.

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Danksagung

Die Autoren danken Dr. Juliane Schreier und Dr. Marc Esser (co.faktor GmbH, Berlin) für die Unterstützung bei der Manuskripterstellung.

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Authors and Affiliations

  1. Klinik und Poliklinik für Urologie, Akkreditiertes Zweitmeinungszentrum Keimzelltumoren, Zertifiziertes Kontinenz- und Beckenboden-Zentrum, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 60, 23538, Lübeck, Deutschland

    Axel S. Merseburger

  2. Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover (MHH), Hannover, Deutschland

    Daniel Sedding

  3. Urologie am Nordkopf, Wolfsburg, Deutschland

    Kai Hüter

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  1. Axel S. Merseburger
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Correspondence to Axel S. Merseburger.

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Interessenkonflikt

A.S. Merseburger: Referenten-, Berater-, Studientätigkeit für Ipsen, Bayer, Pfizer, Novartis, Astellas, Hexal, Ferring, Janssen Cilag, Roche, Wyeth, TEVA, Oncogenex, Medivation. D. Sedding: Referenten-, Berater-, Studientätigkeit für Bayer, Pfizer, Novartis, Ferring, Boehringer Ingelheim, Lilly, Servier, AstraZeneca, Biotronic, Medtronic, Abbott, Berlin Pharma. K. Hüter gibt an, dass kein Interessenkonflikt besteht.

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Merseburger, A.S., Sedding, D. & Hüter, K. Kardiovaskuläre Risikopatienten unter Androgenentzugstherapie. Urologe 55, 218–225 (2016). https://doi.org/10.1007/s00120-015-0013-1

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