From the Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
Epidemiology. 2020 May;31(3):432-440. doi: 10.1097/EDE.0000000000001132.
Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting.
We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease.
The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3).
There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.
雄激素剥夺疗法(ADT)在前列腺癌管理中已被证实具有作用,与各种心血管疾病相关。然而,很少有研究通过 ADT 的类型来研究这些关联,特别是对于新型 ADT,如促性腺激素释放激素(GnRH)拮抗剂地加瑞克。我们在真实环境中研究了不同类型 ADT 与心血管疾病的风险。
我们从苏格兰癌症登记处和全国处方信息系统中确定了 2009 年至 2015 年期间新诊断为前列腺癌的男性,并确定了 ADT。心血管事件基于住院(来自医院记录)或心血管疾病死亡(来自死亡记录)。我们使用 Cox 回归计算了随时间变化的 ADT 暴露下心血管事件的风险比(HR)和 95%置信区间(CI),并将 ADT 使用者与未治疗患者进行了比较,调整了潜在混杂因素,包括先前的心血管疾病。
该队列包含 20216 名前列腺癌患者,随访 73570 人年,期间发生了 3853 例心血管事件。ADT 与心血管事件增加 30%相关(调整后的 HR = 1.3;95%CI = 1.2,1.4)。这反映了 GnRH 激动剂(调整后的 HR = 1.3;95%CI = 1.2,1.4)、地加瑞克(调整后的 HR = 1.5;95%CI = 1.2,1.9)与心血管事件相关的增加,但不是比卡鲁胺单药治疗(调整后的 HR = 1.0;95%CI = 0.82,1.3)。
使用 GnRH 激动剂和地加瑞克会增加心血管疾病的风险,但比卡鲁胺单药治疗不会。这是第一项观察到地加瑞克与心血管风险增加相关的研究,但这种关联的原因尚不清楚,值得进一步研究。