George Gincy, Vikman Hanna, Gedeborg Rolf, Lissbrant Ingela Franck, Garmo Hans, Styrke Johan, Van Hemelrijck Mieke, Stattin Pär
Translational Oncology and Urology Research, King's College Londo, London, UK.
Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
Acta Oncol. 2021 Apr;60(4):459-465. doi: 10.1080/0284186X.2021.1885058. Epub 2021 Feb 19.
Men with prostate cancer (PCa) on gonadotropin-releasing hormone agonists (GnRH) have an increased risk of cardiovascular disease (CVD) compared to men with PCa not on GnRH as well as compared with PCa-free men. Whether the addition of androgen receptor targeted (ART) drugs to GnRH further increases CVD risk, remains to be fully elucidated.
We investigated risk of CVD for men with castration resistant PCa (CRPC) on GnRH plus ART; abiraterone or enzalutamide vs 5,127 and 12,079 respective matched comparator men on GnRH in Prostate Cancer data Base Sweden (PCBaSe) 4.1 between 1 June 2015 and 31 December 2018. PCBaSe links National Prostate Cancer Register of Sweden to other healthcare registries and demographic databases. We conducted multivariable Cox proportional hazard models adjusting for PCa risk category, Charlson comorbidity index (CCI), insulin or statin use, civil status, level of education, history of CVD events and number of CVD drugs, with any incident or fatal CVD as the outcome.
1,310 men were treated with abiraterone and 3,579 with enzalutamide. In multivariable analysis, CVD risk was increased in men on abiraterone (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03-1.38) and in men on enzalutamide (HR: 1.10; 95% CI: 1.01-1.20). Men with a recent CVD (<12 months) including both men on ART as well as comparators had a much higher probability of a new CVD vs men with no prior CVD. CVD risk was mildly increased in men with PCa on GnRH plus abiraterone or enzalutamide vs comparator men on GnRH. Residual confounding and detection bias may at least partly explain this association.
与未使用促性腺激素释放激素激动剂（GnRH）的前列腺癌（PCa）男性以及无PCa的男性相比，使用GnRH的PCa男性患心血管疾病（CVD）的风险增加。在GnRH基础上加用雄激素受体靶向（ART）药物是否会进一步增加CVD风险，仍有待充分阐明。
我们在瑞典前列腺癌数据库（PCBaSe）4.1中，调查了2015年6月1日至2018年12月31日期间，接受GnRH联合ART（阿比特龙或恩杂鲁胺）治疗的去势抵抗性PCa（CRPC）男性的CVD风险，与5127名和12079名分别匹配的接受GnRH治疗的对照男性相比。PCBaSe将瑞典国家前列腺癌登记处与其他医疗保健登记处和人口数据库相链接。我们进行了多变量Cox比例风险模型分析，对PCa风险类别、Charlson合并症指数（CCI）、胰岛素或他汀类药物使用情况、婚姻状况、教育程度、CVD事件史和CVD药物数量进行了调整，以任何新发或致命的CVD作为结局。
1310名男性接受了阿比特龙治疗，3579名男性接受了恩杂鲁胺治疗。在多变量分析中，接受阿比特龙治疗的男性CVD风险增加（风险比（HR）：1.19；95%置信区间（CI）：1.03 - 1.38），接受恩杂鲁胺治疗的男性CVD风险也增加（HR：1.10；95% CI：1.01 - 1.20）。近期患有CVD（<12个月）的男性，包括接受ART治疗的男性以及对照男性，与无既往CVD的男性相比，发生新发CVD的可能性要高得多。与接受GnRH治疗的对照男性相比，接受GnRH联合阿比特龙或恩杂鲁胺治疗的PCa男性CVD风险略有增加。残余混杂因素和检测偏倚可能至少部分解释了这种关联。
