Background:The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.Methods:In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.Results:Because of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59–2.79]; P=0.53).Conclusions:PRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.

中文翻译：

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地加瑞克与亮丙瑞林在前列腺癌患者中的心血管安全性：PRONOUNCE 随机试验的主要结果

背景：与 GnRH 激动剂相比，促性腺激素释放激素 (GnRH) 拮抗剂在患有前列腺癌和已知动脉粥样硬化性心血管疾病的男性中的相对心血管安全性仍然存在争议。方法：在这项国际、多中心、前瞻性、随机、开放标签试验中，男性患有前列腺癌和并发动脉粥样硬化性心血管疾病的患者以 1:1 的比例随机分配接受 GnRH 拮抗剂地加瑞克或 GnRH 激动剂亮丙瑞林 12 个月。主要结局是 12 个月内首次裁定主要不良心血管事件（死亡、心肌梗死或中风）的时间。在计划的 900 名参与者累积之前停止。从 2016 年 5 月 3 日起，至 2020 年 4 月 16 日，共有来自 12 个国家的 113 个地点的 545 名患者被随机选择。研究组之间的基线特征是平衡的。中位年龄为 73 岁，49.8% 患有局限性前列腺癌；26.3%有局部晚期疾病，20.4%有转移性疾病。地加瑞克组 15 例（5.5%）和亮丙瑞林组 11 例（4.1%）发生了主要心血管不良事件（风险比，1.28 [95% CI，0.59–2.79]；P = 0.53)。结论：PRONOUNCE（比较地加瑞克与亮丙瑞林在晚期前列腺癌和心血管疾病患者中的心血管安全性的试验）是第一个前瞻性比较 GnRH 拮抗剂和 GnRH 心血管安全性的国际随机临床试验前列腺癌患者的激动剂。由于参与者和事件的数量少于计划的数量，该研究提前终止，并且未观察到分配到地加瑞克或亮丙瑞林的患者在 1 年时主要不良心血管事件的差异。GnRH 拮抗剂和激动剂的相对心血管安全性仍未解决。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT02663908。