Translational Oncology and Urology Research, King's College London, London, UK.
Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes Hospital University, Rennes, France.
Fundam Clin Pharmacol. 2019 Aug;33(4):479-499. doi: 10.1111/fcp.12454. Epub 2019 Mar 25.
One of the more recently investigated adverse long-term side effects of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer (PCa) is cardiovascular disease (CVD). Studies suggest lower risk of CVD following GnRH antagonists (degarelix) than GnRH agonists. This protocol describes precise codes used to extract variables from five European databases for a study that compares risk of CVD following GnRH agonists and antagonists for PCa. PCa men on primary GnRH agonists or antagonists were identified from the UK THIN (The Health Improvement Network) database, National Health Service (NHS) Scotland, Belgian Cancer Registry (BCR), Dutch PHARMO Database Network and French National Database (SNIIRAM). Cohort entry was defined as date of treatment initiation. CVD event was defined as any first incident or fatal CVD after cohort entry. Readcodes in THIN and ICD codes in NHS Scotland, BCR, PHARMO and SNIIRAM were used to extract variables. Risk of Bias in Non-randomised studies of Interventions (ROBINS-I) tool was used to assess the potential risk of biases in this study. 51 572 men with a median follow-up time of 2 years started on GnRH agonists and 2 417 men with a median follow-up time of 1 year started on GnRH antagonists between 2010 and 2017 in the UK, Scotland, Belgium, the Netherlands and France. Data from five countries improved the study power and internal validity required to compare risk of CVD between GnRH agonists and antagonists, the latter being a fairly new drug with limited data in individual countries.
促性腺激素释放激素（GnRH）激动剂治疗前列腺癌（PCa）的近期研究发现的一种较为严重的长期不良副作用是心血管疾病（CVD）。研究表明，与 GnRH 激动剂相比， GnRH 拮抗剂（地加瑞克）发生 CVD 的风险较低。本方案描述了从五个欧洲数据库中提取变量的精确代码，用于比较 GnRH 激动剂和拮抗剂治疗 PCa 后 CVD 风险的研究。从英国 THIN（健康改善网络）数据库、苏格兰国家卫生服务局（NHS）、比利时癌症登记处（BCR）、荷兰 PHARMO 数据库网络和法国国家数据库（SNIIRAM）中确定了正在接受原发性 GnRH 激动剂或拮抗剂治疗的 PCa 男性。队列入组定义为治疗开始日期。CVD 事件定义为队列入组后任何首次发生或致命性 CVD。THIN 中的 Readcodes 和 NHS 苏格兰、BCR、PHARMO 和 SNIIRAM 中的 ICD 代码用于提取变量。使用非随机干预研究的偏倚风险（ROBINS-I）工具评估本研究中潜在偏倚的风险。2010 年至 2017 年期间，英国、苏格兰、比利时、荷兰和法国共有 51572 名男性中位随访时间为 2 年开始接受 GnRH 激动剂治疗，2417 名男性中位随访时间为 1 年开始接受 GnRH 拮抗剂治疗。来自五个国家的数据提高了研究效能和内部有效性，从而能够比较 GnRH 激动剂和拮抗剂之间 CVD 的风险，后者是一种相对较新的药物，在个别国家的数据有限。
