Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.
Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial.
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DOI：
10.1161/circulationaha.121.056810
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发表时间：
2021-10-19
期刊：
影响因子：
37.8
通讯作者：
Alexander, John H.
中科院分区：
文献类型：
--
作者：
Lopes, Renato D.;Higano, Celestia S.;Slovin, Susan F.;Nelson, Adam J.;Bigelow, Robert;Sorensen, Per S.;Melloni, Chiara;Goodman, Shaun G.;Evans, Christopher P.;Nilsson, Jan;Bhatt, Deepak L.;Clarke, Noel W.;Olesen, Tine K.;Doyle-Olsen, Belinda T.;Kristensen, Henriette;Arney, Lauren;Roe, Matthew T.;Alexander, John H.
关键词：
对于患有前列腺癌和已知动脉粥样硬化性心血管疾病 (ASCVD) 的男性，促性腺激素释放激素 (GnRH) 拮抗剂与 GnRH 激动剂相比的相对心血管安全性仍存在争议。在这项国际、多中心、前瞻性、随机、开放标签试验中，患有前列腺癌并伴有 ASCVD 的男性以 1:1 的比例随机接受 GnRH 拮抗剂地加瑞克或 GnRH 激动剂亮丙瑞林治疗 12 个月。主要结局是 12 个月内首次判定发生重大不良心血管事件 (MACE)（死亡、心肌梗死或中风的复合事件）的时间。由于入组速度慢于预期且主要结局事件少于预期，在计划的 900 名参与者完成之前就停止了入组。从2016年5月3日到2020年4月16日，来自12个国家113个地点的总共545名患者被随机分组。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% 患有局部晚期疾病，20.4% 患有转移性疾病。分配到地加瑞克的 15 名患者 (5.5%) 和分配到亮丙瑞林的 11 名患者 (4.1%) 发生 MACE（风险比 [HR] 1.28，95% 置信区间 [CI] 0.59–2.79；p=0.53）。 PRONOUNCE 是第一个国际随机临床试验，前瞻性比较 GnRH 拮抗剂和 GnRH 激动剂在前列腺癌患者中的心血管安全性。该研究因参与者和事件数量少于计划而提前终止，并且未观察到分配至地加瑞克或亮丙瑞林的患者之间 1 年时的 MACE 差异。 GnRH 拮抗剂和激动剂的相对心血管安全性仍未解决。 ClinicalTrials.gov (NCT02663908)。
The relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease (ASCVD) remains controversial. In this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant ASCVD were randomized 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 (MACE) (composite of death, myocardial infarction, or stroke) through 12 months. Due to slower than projected enrollment and fewer than projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From 3 May 2016 to 16 April 2020, a total of 545 patients from 113 sites across 12 countries were randomized. 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. MACE occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) assigned to leuprolide (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.59–2.79; p=0.53). PRONOUNCE 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 due to smaller than planned number of participants and events and no difference in MACE at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. ClinicalTrials.gov (NCT02663908).