Crawford E David, Hafron Jason M, Debruyne Frans, Wallis Christopher, Chang Steven, Garnick Marc B
University of California San Diego, Koman Family Outpatient Pavilion, San Diego, California.
Michigan Institute of Urology, Troy, Michigan.
J Urol. 2024 Jan;211(1):63-70. doi: 10.1097/JU.0000000000003721. Epub 2023 Oct 5.
Luteinizing hormone-releasing hormone (LHRH) agonists are believed to have higher cardiovascular risk relative to gonadotropin-releasing hormone (GnRH) antagonists. However, previous studies have not consistently demonstrated this. We used real-world clinical practice data to evaluate differences in major adverse cardiovascular events (MACE) risk between LHRH agonists compared to a GnRH antagonist following androgen deprivation therapy (ADT) initiation.
We performed a retrospective analysis of data in the Decision Resources Group (now Clarivate) Real World Evidence repository, which represents >300 million US patients from 1991 to 2020 across all US regions. Patients with prostate cancer who received at least 1 injection of ADT were included. The risks of MACE and all-cause mortality as independent endpoints were evaluated, Kaplan-Meier curves were constructed, and associations between MACE and all available confounding risk factors were evaluated by Cox regression analysis using Statistical Package for the Social Sciences.
A total of 45,059 men with prostate cancer treated with ADT were analyzed. Overall, the risks of MACE and all-cause mortality were slightly lower in the first year after ADT initiation compared to subsequent years. MACE risk was higher for the GnRH antagonist compared to LHRH agonists (HR=1.62; 95% CI 1.21-2.18, = .001). The risk of all-cause mortality was also higher for the GnRH antagonist vs LHRH agonists (HR=1.87; 95% CI 1.39-2.51, < .001).
The adjusted incidence of MACE was higher for men treated with the GnRH antagonist compared to the LHRH agonists. The demographic and risk factors with the greatest impact on MACE risk were higher age, baseline metastasis, oncology (vs urology) setting, personal MACE history, antagonist (vs agonist), tobacco history, White (vs Black) race, and lower BMI.
与促性腺激素释放激素（GnRH）拮抗剂相比，促黄体生成素释放激素（LHRH）激动剂被认为具有更高的心血管风险。然而，既往研究并未始终如一地证实这一点。我们使用真实世界临床实践数据来评估雄激素剥夺治疗（ADT）开始后，LHRH激动剂与GnRH拮抗剂相比在主要不良心血管事件（MACE）风险上的差异。
我们对决策资源集团（现为科睿唯安）真实世界证据库中的数据进行了回顾性分析，该数据库代表了1991年至2020年美国所有地区超过3亿美国患者。纳入接受至少1次ADT注射的前列腺癌患者。评估MACE风险和全因死亡率作为独立终点，构建Kaplan-Meier曲线，并使用社会科学统计软件包通过Cox回归分析评估MACE与所有可用混杂风险因素之间的关联。
共分析了45059例接受ADT治疗的前列腺癌男性患者。总体而言，ADT开始后的第一年，MACE和全因死亡率风险相较于随后几年略低。与LHRH激动剂相比，GnRH拮抗剂的MACE风险更高（风险比[HR]=1.62；95%置信区间[CI]为1.21-2.18，P=.001）。GnRH拮抗剂的全因死亡率风险也高于LHRH激动剂（HR=1.87；95%CI为1.39-2.51，P<.001）。
与LHRH激动剂相比，接受GnRH拮抗剂治疗的男性患者经调整后的MACE发病率更高。对MACE风险影响最大的人口统计学和风险因素包括年龄较大、基线转移、肿瘤学（与泌尿外科学相比）环境、个人MACE病史、拮抗剂（与激动剂相比）、吸烟史、白人（与黑人相比）种族以及较低的体重指数。
