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他汀类药物各亚组与前列腺癌之间的建议独特关联。

The Suggested Unique Association Between the Various Statin Subgroups and Prostate Cancer.

机构信息

Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

出版信息

Eur Urol Focus. 2021 May;7(3):537-545. doi: 10.1016/j.euf.2020.06.005. Epub 2020 Jun 30.

Abstract

BACKGROUND

The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a "drug family" overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins.

OBJECTIVE

To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy.

DESIGN, SETTING, AND PARTICIPANTS: This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models.

RESULTS AND LIMITATIONS

Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9-47.5%), a 20% (95% CI 10-28%), and an 18% (95% CI 6.1-27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2-31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies.

CONCLUSIONS

Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration.

PATIENT SUMMARY

Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.

摘要

背景

各种药物在前列腺癌(PCa)中的化学预防作用引起了关注。具体来说,他汀类药物对 PCa 发病率的潜在影响已经得到了研究,但仅仅作为一个“药物家族”,忽略了其两个主要亚组(亲水性和疏水性他汀类药物)独特的药理学特性。

目的

评估他汀类药物亚组对 PCa 特异性死亡率(PCSM)、PCa 诊断和再次进行前列腺活检的影响。

设计、地点和参与者:这是一项基于人群的队列研究,在安大略省确定了所有年龄≥66 岁、有单次阴性前列腺活检史(代表有 PCa 风险的健康男性)的男性,这些男性在研究前没有使用任何分析药物,中位随访时间为 9.42 年(四分位间距 8.03 年)。

结局测量和统计分析

使用多变量原因特异性风险模型和时间依赖性协变量,分析疏水性和亲水性他汀类药物与所有研究结局的关系。其他可能的化学预防药物(包括α-阻滞剂、5-α-还原酶抑制剂和质子泵抑制剂)、年龄、农村/城市、合并症和研究纳入年份被纳入模型。

结果和局限性

共有 21512 名男性被确定。11401 名患者(50.3%)服用了他汀类药物,5184 名男性(24.1%)被诊断为 PCa,805 名(3.7%)死于该病。共有 7556 名患者(35.1%)再次接受了活检。亲水性他汀类药物的任何使用与 PCSM(95%置信区间 [CI] 12.9-47.5%)、再次前列腺活检(95%CI 10-28%)和 PCa 诊断(95%CI 6.1-27.3%)的风险降低 32.4%、20%和 18%相关。疏水性他汀类药物与 PCSM 降低 17%(95%CI 2-31%)相关。该研究受到其回顾性、选择偏差和伴随的健康管理数据库不准确的限制。

结论

使用任何他汀类药物可能与 PCSM 风险降低相关,亲水性他汀类药物与 PCa 诊断率降低的相关性更强。在男性中优先选择一种他汀类药物亚组而不是另一种亚组需要进一步探索。

患者总结

使用任何他汀类药物可能与降低死于前列腺癌的概率相关。亲水性他汀类药物(瑞舒伐他汀和普伐他汀)也可能与 66 岁及以上男性接受额外前列腺活检和诊断为前列腺癌的风险降低呈更积极的相关性。

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