Mackenzie Isla S, Morant Steven V, Wei Li, Thompson Alastair M, MacDonald Thomas M
Medicines Monitoring Unit (MEMO), Division of Molecular and Clinical Medicine, University of Dundee, Dundee, DD1 9SY, UK.
School of Pharmacy, University College London, Gower Street, London, WC1E 6BT, UK.
Br J Clin Pharmacol. 2017 Mar;83(3):653-663. doi: 10.1111/bcp.13152. Epub 2016 Nov 12.
Spironolactone is widely used to treat heart failure, hypertension and liver disease with increased usage in recent years. Spironolactone has endocrine effects that could influence cancer risks and historical reports suggest possible links with increased risk of certain types of cancer. The aim of this study was to assess the effect of spironolactone exposure on cancer incidence.
A pharmacoepidemiological propensity score-matched cohort study was performed to assess the effect of spironolactone exposure on cancer incidence. Cox proportional hazards models were used to analyse time to first diagnosis of each prespecified cancer and hazard ratios for spironolactone exposure are presented. The setting for the study was UK primary care using the Clinical Practice Research Datalink. The participants were 74 272 patients exposed to spironolactone between 1986 and 2013, matched 1:2 with unexposed controls. The prespecified primary outcomes were the first incidence of ovarian, endometrial, pancreatic, colorectal, prostate, renal cell, pharyngeal and thyroid cancers, and myelomonoblastic/-cytic leukaemias. Secondary outcomes were the remaining 27 types of cancer.
There was no evidence of an increased risk of any cancer associated with spironolactone use. Spironolactone use was associated with a significantly lower risk of prostate cancer (hazard ratio 0.69; 95% confidence interval 0.60-0.80, P < 0.001).
In this study, spironolactone use was associated with a lower incidence of prostate cancer, the most common cancer in men in the UK. The possible mechanisms and clinical implications merit further investigation.
螺内酯广泛用于治疗心力衰竭、高血压和肝脏疾病,近年来其使用量有所增加。螺内酯具有内分泌效应,可能影响癌症风险,既往报道提示其与某些类型癌症风险增加可能存在关联。本研究旨在评估螺内酯暴露对癌症发病率的影响。
开展一项药物流行病学倾向评分匹配队列研究,以评估螺内酯暴露对癌症发病率的影响。采用Cox比例风险模型分析每种预先指定癌症的首次诊断时间,并给出螺内酯暴露的风险比。研究采用英国初级医疗保健机构的临床实践研究数据链。参与者为1986年至2013年间暴露于螺内酯的74272例患者,与未暴露的对照按1:2进行匹配。预先指定的主要结局为卵巢癌、子宫内膜癌、胰腺癌、结直肠癌、前列腺癌、肾细胞癌、咽喉癌和甲状腺癌以及骨髓单核细胞/粒细胞白血病的首次发病情况。次要结局为其余27种癌症类型。
没有证据表明使用螺内酯会增加任何癌症的风险。使用螺内酯与前列腺癌风险显著降低相关(风险比0.69;95%置信区间0.60 - 0.80,P < 0.001)。
在本研究中,使用螺内酯与前列腺癌发病率较低相关,前列腺癌是英国男性中最常见的癌症。其可能的机制和临床意义值得进一步研究。