Patel Savan, Zhu Kexin, Dave Chintan V, Ghajar Mina, Zhang Yingting, Saraiya Biren, Bandera Elisa V, Khosrow-Khavar Farzin
Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; Department of Biostatistics and Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Healthcare Policy and Aging Research, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Eur Urol Oncol. 2025 Apr;8(2):510-519. doi: 10.1016/j.euo.2024.09.004. Epub 2024 Sep 28.
Gonadotropin-releasing hormone (GnRH) antagonists and agonists are cornerstone treatments in prostate cancer. However, evidence regarding the comparative cardiovascular safety of these drugs from clinical trials is inconclusive. The objective of this study was to systematically assess the risk of adverse cardiovascular events of GnRH antagonists compared with GnRH agonists across real-world evidence studies.
We conducted a systematic search of PubMed, Embase, Cochrane Library, Scopus, and Web of Science (2008-2023). We included real-world evidence studies comparing the risk of cardiovascular outcomes of GnRH antagonists with those of GnRH agonists among patients with prostate cancer. We conducted a meta-analysis of effect estimates across studies at a low or moderate risk of bias, assessed via the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool, using random-effect models.
Among ten included studies, four were classified as having a moderate and six as having a serious risk of bias. Across three studies at a moderate risk of bias in the primary analysis, degarelix was associated with an increased risk (pooled relative risk [RR]: 1.31, 95% confidence interval [CI]: 1.14-1.51) of major adverse cardiovascular events (MACEs). An augmented risk was observed in two studies among patients with a history of cardiovascular disease (pooled RR: 1.31, 95% CI: 1.11-1.56) compared with one study among patients without a history of cardiovascular disease (RR: 1.15, 95% CI: 0.83-1.59).
Real-world evidence studies indicate that degarelix, compared with GnRH agonists, is associated with a modest increased risk of MACEs, particularly among patients with a history of cardiovascular disease. However, residual confounding due to the treatment of high-risk patients with degarelix may account for these findings. Additional large studies with detailed data on tumor characteristics and cardiovascular risk factors are needed to confirm these findings.
In this systematic evaluation of evidence among patients diagnosed with prostate cancer in routine care, degarelix was associated with higher cardiovascular adverse outcomes than gonadotropin-releasing hormone agonists.
促性腺激素释放激素（GnRH）拮抗剂和激动剂是前列腺癌的基础治疗药物。然而，来自临床试验的关于这些药物相对心血管安全性的证据尚无定论。本研究的目的是通过真实世界证据研究，系统评估GnRH拮抗剂与GnRH激动剂相比发生心血管不良事件的风险。
我们对PubMed、Embase、Cochrane图书馆、Scopus和科学网（2008 - 2023年）进行了系统检索。纳入了比较前列腺癌患者中GnRH拮抗剂与GnRH激动剂心血管结局风险的真实世界证据研究。我们使用随机效应模型，对通过干预性非随机研究的偏倚风险（ROBINS - I）工具评估为低或中度偏倚风险的研究中的效应估计值进行了荟萃分析。
在纳入的十项研究中，四项被归类为具有中度偏倚风险，六项被归类为具有严重偏倚风险。在主要分析中，三项具有中度偏倚风险的研究显示，地加瑞克与主要不良心血管事件（MACE）风险增加相关（合并相对风险[RR]：1.31，95%置信区间[CI]：1.14 - 1.51）。与一项针对无心血管疾病史患者的研究（RR：1.15，95% CI：0.83 - 1.59）相比，两项针对有心血管疾病史患者的研究观察到风险增加（合并RR：1.31，95% CI：1.11 - 1.56）。
真实世界证据研究表明，与GnRH激动剂相比，地加瑞克与MACE风险适度增加相关，尤其是在有心血管疾病史的患者中。然而，使用地加瑞克治疗高危患者导致的残余混杂因素可能解释了这些发现。需要更多关于肿瘤特征和心血管危险因素详细数据的大型研究来证实这些发现。
在本次对常规护理中诊断为前列腺癌患者的证据进行的系统评估中，地加瑞克与比促性腺激素释放激素激动剂更高的心血管不良结局相关。
