Cardio-oncology Research Unit, Cardiovascular Analytics Group, China-UK Collaboration, Hong Kong, China.
Cardio-oncology Research Unit, Cardiovascular Analytics Group, China-UK Collaboration, Hong Kong, China; Division of Urology, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Clin Oncol (R Coll Radiol). 2023 Jun;35(6):e376-e383. doi: 10.1016/j.clon.2023.03.014. Epub 2023 Mar 29.
Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists.
Patients with PCa receiving GnRH agonists or antagonists during 2013-2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACE, i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups.
In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0-81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7-5.0 years), 1115 patients (45.0%) had MACE and 344 (13.9%) had MACE. GnRH agonist users had lower risks of MACE (Log-rank P < 0.001) and MACE (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACE: Log-rank P = 0.308; MACE: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACE (Log-rank P < 0.001) and MACE (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACE: Log-rank P = 0.569; MACE: Log-rank P = 0.615).
GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors.
促性腺激素释放激素（GnRH）激动剂和拮抗剂是前列腺癌（PCa）治疗的关键药物，它们在心血管安全性方面可能存在差异。本前瞻性队列研究旨在比较 GnRH 激动剂和拮抗剂之间的长期心血管风险。
在香港，2013 年至 2021 年间，确定了接受 GnRH 激动剂或拮抗剂治疗的 PCa 患者。排除了接受<6 个月处方、药物转换、基线前列腺特异性抗原水平缺失或既往中风或心肌梗死的患者。患者随访至 2021 年 9 月。主要结局为重大不良心血管事件（MACE），如 PRONOUNCE 试验（MACE）中的定义，即全因死亡率、中风和心肌梗死的复合结局。次要结局为 MACE，即心血管死亡率、中风和心肌梗死的复合结局。采用逆概率治疗加权法在组间平衡协变量。采用对数秩检验比较组间主要结局的累积无事件生存率。
共分析了 2479 例患者（162 例 GnRH 拮抗剂使用者和 2317 例 GnRH 激动剂使用者；中位年龄 75.0 岁，四分位间距 68.0-81.6 岁）。逆概率治疗加权法在组间实现了良好的协变量平衡。中位随访时间为 3.0 年（四分位间距 1.7-5.0 年），1115 例患者（45.0%）发生 MACE，344 例（13.9%）发生 MACE。GnRH 激动剂使用者发生 MACE 的风险较低（对数秩 P<0.001）和 MACE（对数秩 P=0.027）。然而，在随访 1 年内未观察到差异（MACE：对数秩 P=0.308；MACE：对数秩 P=0.357）。在基线无心血管危险因素的患者中，GnRH 激动剂使用者发生 MACE（对数秩 P<0.001）和 MACE（对数秩 P=0.001）的风险较低，而在存在此类危险因素的患者中未观察到差异（MACE：对数秩 P=0.569；MACE：对数秩 P=0.615）。
在亚洲 PCa 患者中，GnRH 拮抗剂与 GnRH 激动剂相比，长期心血管风险较高，而非短期风险较高，特别是在无已知心血管危险因素的患者中。
