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[雄激素剥夺治疗患者的心血管副作用:促性腺激素释放激素拮抗剂的优势?最新进展]

[Cardiovascular side effects in patients undergoing androgen deprivation therapy: superiority of gonadotropin-releasing hormone antagonists? An update].

作者信息

von Amsberg Gunhild, Thiele Holger, Merseburger Axel

机构信息

II. medizinische Klinik, Onkologisches Zentrum und Martini-Klinik, Universitätsklinik Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland.

Herzzentrum Leipzig, Universitätsklinik für Kardiologie, Leipzig, Deutschland.

出版信息

Urologe A. 2021 Nov;60(11):1450-1457. doi: 10.1007/s00120-021-01583-9. Epub 2021 Jul 2.

DOI:10.1007/s00120-021-01583-9
PMID:34213627
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8568757/
Abstract

BACKGROUND

Androgen deprivation therapy (ADT) plays a crucial role in treatment of advanced prostate cancer (PCa). The additional application of new drugs results in prolonged overall survival, both in the hormone sensitive and castration resistant state. Consequently, the long-term use of ADT moves potential side effects into the focus of interest. In this context special consideration must be given to cardiovascular events.

OBJECTIVES

Review of current evidence on potential differences regarding the cardiovascular risk profile of gonadotropin-releasing hormone (GnRH) agonists compared to GnRH antagonists.

METHODS

Narrative review based on an expert consensus supported by a literature search in PubMed (MEDLINE) and the abstract databases of ASCO and ESMO was conducted for publications published between January 2015 and January 2021. Significant meta-analyses, randomized controlled trials (RCTs) and real-world data (RWD) revealing relevant results for clinical practice were taken into account. Selection of studies was performed based on the clinical relevance for everyday practice.

RESULTS

The search yielded three relevant meta-analyses, two prospective RCTs as well as three RWD publications that are of importance for clinical practice. Overall, a decreased incidence of cardiovascular events was reported for GnRH antagonists compared to GnRH agonists. Only one RWD publication described comparable rates of complications for both drug classes.

CONCLUSION

GnRH antagonists have a lower risk of treatment related cardiovascular events compared to GnRH agonists. Risks should be minimized by taking known cardiovascular risk factors into account before initiating therapy.

摘要

背景

雄激素剥夺疗法(ADT)在晚期前列腺癌(PCa)的治疗中起着关键作用。新药的额外应用可延长激素敏感和去势抵抗状态下的总生存期。因此,ADT的长期使用使潜在的副作用成为关注焦点。在此背景下,必须特别考虑心血管事件。

目的

综述关于促性腺激素释放激素(GnRH)激动剂与GnRH拮抗剂在心血管风险特征方面潜在差异的现有证据。

方法

基于专家共识进行叙述性综述,并在PubMed(MEDLINE)以及美国临床肿瘤学会(ASCO)和欧洲肿瘤内科学会(ESMO)的摘要数据库中进行文献检索,纳入2015年1月至2021年1月发表的文献。考虑了具有临床实践相关重要结果的显著荟萃分析、随机对照试验(RCT)和真实世界数据(RWD)。根据日常临床实践的相关性进行研究选择。

结果

检索得到三项相关的荟萃分析、两项前瞻性RCT以及三项对临床实践具有重要意义的RWD出版物。总体而言,与GnRH激动剂相比,GnRH拮抗剂的心血管事件发生率有所降低。只有一篇RWD出版物描述了两类药物的并发症发生率相当。

结论

与GnRH激动剂相比,GnRH拮抗剂治疗相关心血管事件的风险更低。在开始治疗前,应考虑已知的心血管危险因素,将风险降至最低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28a6/8568757/5ff6cc6d628a/120_2021_1583_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28a6/8568757/5ff6cc6d628a/120_2021_1583_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28a6/8568757/5ff6cc6d628a/120_2021_1583_Fig1_HTML.jpg

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本文引用的文献

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Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD012548. doi: 10.1002/14651858.CD012548.pub2.
2
The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer.促性腺激素释放激素拮抗剂对前列腺癌男性的心血管影响。
Eur Heart J Cardiovasc Pharmacother. 2022 May 5;8(3):253-262. doi: 10.1093/ehjcvp/pvab005.
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Circulating Vitamin D and Selenium Levels and Outcome in Prostate Cancer Patients: Lessons from the MARTINI-Lifestyle Cohort.
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Eur Urol Focus. 2021 Sep;7(5):973-979. doi: 10.1016/j.euf.2020.12.005. Epub 2021 Jan 3.
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Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice.GnRH 激动剂和拮抗剂的心血管风险概况:来自英国普通实践的真实世界分析。
World J Urol. 2021 Feb;39(2):307-315. doi: 10.1007/s00345-020-03433-3. Epub 2020 Sep 26.
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Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.奥拉帕利治疗转移性去势抵抗性前列腺癌的生存获益。
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6
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Prostate Cancer Prostatic Dis. 2021 Mar;24(1):177-185. doi: 10.1038/s41391-020-0264-9. Epub 2020 Jul 31.
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