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抗高血压药物与芬兰根治性前列腺切除术后前列腺癌生存:一项全国性队列研究。

Antihypertensive drugs and prostate cancer survival after radical prostatectomy in Finland-A nationwide cohort study.

机构信息

Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.

Department of Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

出版信息

Int J Cancer. 2019 Feb 1;144(3):440-447. doi: 10.1002/ijc.31802. Epub 2018 Nov 5.

Abstract

Antihypertensive (anti-HT) drugs targeting renin-angiotensin-aldosterone (RAA)- system have been associated with improved prostate cancer (PCa)-specific survival. Challenge is that often multiple drugs are used simultaneously. We evaluated the association between use of anti-HT drugs and PCa survival among 14,422 surgically treated Finnish PCa patients. Information on drug purchases was obtained from a national prescription database. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of PCa death and initiation of androgen deprivation therapy (ADT) with adjustment for age, tumor extent, use of statins and for Charlson Comorbidity Index. Angiotensin-converting enzyme (ACE)- inhibitors, angiotensin- receptor (ATR)-blockers, diuretics, calcium-channel blockers, beta-blockers and other anti-HT drugs were analyzed as separate time-dependent variables to model simultaneous use. Overall anti-HT drugs were associated with an increased risk of PCa death. Conversely use of ATR-blockers was associated with decreased risk of PCa death (HR: 0.43, 95% CI: 0.26-0.72 and HR: 0.60, 95% CI 0.37-0.97 for pre- and post-diagnostic use). Similar risk decrease was not observed in other drug groups. Anti-HT drugs were also associated with an increased risk of starting ADT, with the exception of ATR-blockers (HR: 0.81 CI:0.71-0.92). ATR- blockers differ from other anti-HT drugs as the survival is better in users of this drug group. The result partly supports the role of RAA system in PCa progression. Nevertheless, the risk decrease was not observed in ACE-inhibitor users. Further research is needed to elucidate the molecular mechanism for the potential anticancer effect of ATR- blockers.

摘要

抗高血压(anti-HT)药物靶向肾素-血管紧张素-醛固酮(RAA)系统已与改善前列腺癌(PCa)特异性生存相关。挑战在于通常同时使用多种药物。我们评估了 14422 例芬兰接受手术治疗的 PCa 患者中使用抗 HT 药物与 PCa 生存之间的关系。药物购买信息来自国家处方数据库。我们使用 Cox 回归计算风险比(HR)和 95%置信区间(95%CI),以调整年龄、肿瘤程度、使用他汀类药物和 Charlson 合并症指数后,评估 PCa 死亡和开始雄激素剥夺治疗(ADT)的风险。血管紧张素转换酶(ACE)抑制剂、血管紧张素受体(ATR)阻滞剂、利尿剂、钙通道阻滞剂、β受体阻滞剂和其他抗 HT 药物被分析为单独的时间依赖性变量,以模拟同时使用。总体而言,抗 HT 药物与 PCa 死亡风险增加相关。相反,ATR 阻滞剂的使用与 PCa 死亡风险降低相关(诊断前和诊断后使用的 HR:0.43,95%CI:0.26-0.72 和 HR:0.60,95%CI 0.37-0.97)。在其他药物组中未观察到类似的风险降低。除 ATR 阻滞剂外,抗 HT 药物还与开始 ADT 的风险增加相关(HR:0.81 CI:0.71-0.92)。ATR 阻滞剂与其他抗 HT 药物不同,因为该药物组的使用者的生存率更好。该结果部分支持 RAA 系统在 PCa 进展中的作用。然而,ACE 抑制剂使用者未观察到风险降低。需要进一步研究阐明 ATR 阻滞剂潜在抗癌作用的分子机制。

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