Coronary Plaque Progression After Androgen Deprivation Therapy in Men With Prostate Cancer: A Randomized Clinical Trial.

Recent studies have yielded conflicting results regarding the CV safety of gonadotropin-releasing hormone (GnRH) agonists vs antagonists.

最近的研究对于促性腺激素释放激素（GnRH）激动剂与拮抗剂的心血管安全性产生了相互矛盾的结果。

Background

To test the hypothesis that ADT is associated with accelerated coronary atherosclerosis and is more prominent with a GnRH agonist compared with a GnRH antagonist.

为了验证雄激素剥夺治疗（ADT）与加速冠状动脉粥样硬化有关，并且与促性腺激素释放激素（GnRH）激动剂相比，使用GnRH拮抗剂时更为显著的假设。

DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized clinical trial was conducted at 4 centers affiliated with a single academic institution in Atlanta, Georgia.

设计、设置和参与者：这项开放标签的随机临床试验在乔治亚州亚特兰大的一所学术机构附属的4个中心进行。

Participants were men with nonmetastatic PCa without prior ADT exposure receiving pelvic radiotherapy with ADT of 6 months duration or longer.

参与者为未接受过雄激素剥夺治疗（ADT）的非转移性前列腺癌（PCa）男性患者，接受盆腔放疗并接受6个月或更长时间的ADT。

Patients were randomly assigned 1:1 to either the GnRH agonist leuprolide or the GnRH antagonist relugolix.

患者按1:1的比例随机分配至GnRH激动剂亮丙瑞林组或GnRH拮抗剂瑞鲁曲普组。

Trial enrollment was completed between June 16, 2022, and March 6, 2024.

试验招募工作已于2022年6月16日至2024年3月6日完成。

Data analysis was completed between March 31, 2025, and June 23, 2025.

数据分析工作已于2025年3月31日至2025年6月23日完成。

intervention

Pelvic radiotherapy plus either GnRH agonist leuprolide or GnRH antagonist relugolix.

骨盆放射治疗联合使用GnRH激动剂亮丙瑞林或GnRH拮抗剂瑞鲁戈利克斯。

main_outcomes_and_measures

The primary end point was change in coronary artery total plaque volume (TPV), measured by coronary computed tomographic angiography completed at baseline and 12 months after ADT initiation.

主要终点是冠状动脉总斑块体积（TPV）的变化，通过在基线和ADT启动后12个月完成的冠状动脉计算机断层扫描血管造影测量。

The secondary end point was change in coronary artery noncalcified plaque volume (NCPV).

次要终点是冠状动脉非钙化斑块体积(NCPV)的变化。

Other outcome measures included change in calcified plaque volume (CPV) and low-attenuation plaque volume (LAPV).

其他的结果指标包括钙化斑块体积(CPV)的变化和低密度斑块体积(LAPV)的变化。

Results

Of 65 men enrolled, 62 (31 in each arm) completed all study procedures for analysis.

在入组的65名男性中，有62名（每组31名）完成了所有研究程序以供分析。

Mean (SD) age was 68.5 (8.5) years, and 35 of 62 participants (56%) were taking statins.

平均（标准差）年龄为68.5（8.5）岁，62名参与者中有35名（56%）正在服用他汀类药物。

Compared with relugolix, leuprolide was associated with a significantly greater 12-month increase in TPV (estimated difference, +68.9 mm3; 95% CI, 23.2-114.5 mm3; P = .02) and NCPV (+64.5 mm3; 95% CI, 31.6-97.3 mm3; P = .004) after adjustment for baseline plaque volume, age, and statin use.

与 relugolix 相比，leuprolide 与 12 个月 TPV 的显著增加有关（估计差异，+68.9 mm3；95% 置信区间，23.2-114.5 mm3；P = .02）以及在调整基线斑块体积、年龄和他汀类药物使用后的 NCPV（+64.5 mm3；95% 置信区间，31.6-97.3 mm3；P = .004）。

There was no significant difference in 12-month change in CPV or LAPV between patients treated with leuprolide vs relugolix.

在使用 leuprolide 与 relugolix 治疗的患者之间，12 个月 CPV 或 LAPV 的变化没有显著差异。

conclusions_and_relevance

In this randomized clinical trial in men with localized PCa treated with radiation plus ADT, the GnRH agonist leuprolide was associated with greater coronary plaque progression within 12 months compared with the GnRH antagonist relugolix.

在这项针对接受放射治疗加抗雄激素治疗（ADT）的局限性前列腺癌（PCa）男性患者的随机临床试验中，促性腺激素释放激素（GnRH）激动剂亮丙瑞林与在12个月内冠状动脉斑块进展更大相关，与GnRH拮抗剂relugolix相比。

This change was driven by an increase in noncalcified plaque volume and may be mediating ADT-associated CV risk.

这种变化是由非钙化斑块体积的增加所驱动的，可能是介导ADT相关的心血管风险。

trial_registration

ClinicalTrials.gov Identifier: NCT05320406.

临床试验注册号：NCT05320406。