Spironolactone use and risk of incident cancers: a retrospective, matched cohort study

Isla S. Mackenzie; Steven V. Morant; Li Wei; Alastair M. Thompson; Thomas M. MacDonald

doi:10.1111/bcp.13152

Spironolactone use and risk of incident cancers: a retrospective, matched cohort study

Isla S. Mackenzie (Lead / Corresponding author), Steven V. Morant, Li Wei, Alastair M. Thompson, Thomas M. MacDonald

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Abstract

Aims: 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.
Methods: 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 pre-specified cancer and hazard ratios (HR) for spironolactone exposure are presented.
Setting: UK primary care using the Clinical Practice Research Datalink (CPRD).
Participants: 74,272 patients exposed to spironolactone between 1986 and 2013, matched 1:2 with unexposed controls.
Main outcome measures: The pre-specified 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.
Results: 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 (HR 0.69; 95% CI 0.60-0.80, p<0.001).
Conclusions: 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.

Original language	English
Pages (from-to)	653-663
Number of pages	11
Journal	British Journal of Clinical Pharmacology
Volume	83
Issue number	3
Early online date	13 Oct 2016
DOIs	https://doi.org/10.1111/bcp.13152
Publication status	Published - 14 Feb 2017

Keywords

Spironolactone
Cancer
Pharmacoepidemiology
Cohort study
Prostate

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10.1111/bcp.13152Licence: CC BY-NC-ND

Publisher final version
© 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Final published version, 503 KBLicence: CC BY-NC-ND

MacDonald, Thomas
- Cardiovascular Research - Emeritus Professor of Clin Pharma and Pharmacoepidemiology
Person: Honorary
Mackenzie, Isla
- Cardiovascular Research - Clinical Professor (Teaching and Research) of Cardiovascular Medicine
Person: Academic

Cite this

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title = "Spironolactone use and risk of incident cancers: a retrospective, matched cohort study",

abstract = "Aims: 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.Methods: 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 pre-specified cancer and hazard ratios (HR) for spironolactone exposure are presented.Setting: UK primary care using the Clinical Practice Research Datalink (CPRD).Participants: 74,272 patients exposed to spironolactone between 1986 and 2013, matched 1:2 with unexposed controls.Main outcome measures: The pre-specified 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.Results: 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 (HR 0.69; 95% CI 0.60-0.80, p<0.001). Conclusions: 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.",

keywords = "Spironolactone, Cancer, Pharmacoepidemiology, Cohort study, Prostate",

author = "Mackenzie, {Isla S.} and Morant, {Steven V.} and Li Wei and Thompson, {Alastair M.} and MacDonald, {Thomas M.}",

note = "The study was funded by a grant from the Anonymous Trust. ",

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T2 - a retrospective, matched cohort study

AU - Mackenzie, Isla S.

AU - Morant, Steven V.

AU - Wei, Li

AU - Thompson, Alastair M.

AU - MacDonald, Thomas M.

N1 - The study was funded by a grant from the Anonymous Trust.

PY - 2017/2/14

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N2 - Aims: 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.Methods: 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 pre-specified cancer and hazard ratios (HR) for spironolactone exposure are presented.Setting: UK primary care using the Clinical Practice Research Datalink (CPRD).Participants: 74,272 patients exposed to spironolactone between 1986 and 2013, matched 1:2 with unexposed controls.Main outcome measures: The pre-specified 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.Results: 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 (HR 0.69; 95% CI 0.60-0.80, p<0.001). Conclusions: 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.

AB - Aims: 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.Methods: 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 pre-specified cancer and hazard ratios (HR) for spironolactone exposure are presented.Setting: UK primary care using the Clinical Practice Research Datalink (CPRD).Participants: 74,272 patients exposed to spironolactone between 1986 and 2013, matched 1:2 with unexposed controls.Main outcome measures: The pre-specified 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.Results: 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 (HR 0.69; 95% CI 0.60-0.80, p<0.001). Conclusions: 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.

KW - Spironolactone

KW - Cancer

KW - Pharmacoepidemiology

KW - Cohort study

KW - Prostate

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EP - 663

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 3

ER -

Spironolactone use and risk of incident cancers: a retrospective, matched cohort study

Abstract

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MacDonald, Thomas

Mackenzie, Isla

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