Impact of Spironolactone Exposure on Prostate Cancer Incidence Amongst Men with Heart Failure: A Pharmacoepidemiologic Study.

AIM: Aldosterone has been found to influence cancer cell growth, cell cycle regulation, and cell migration, including in prostate cancer cells. Spironolactone is an aldosterone antagonist used for managing chronic heart failure (HF) with known antiandrogenic effects. We examined the effect of spironolactone exposure amongst men with HF on the incidence of prostate cancer.

METHODS: This retrospective cohort study utilized provincial clinical and administrative databases from the Manitoba Centre for Health Policy. Incident cases of prostate cancer were identified from the provincial cancer registry, and spironolactone exposure was quantified from pharmacare databases. A multivariable proportional hazards model was used to assess the time dependent impact of spironolactone exposure on prostate cancer incidence.

RESULTS: A total of 18,562 men with newly diagnosed HF from 2007 to 2015 with a median age of 72 (IQR: 61 to 81) and a median follow-up from HF diagnosis to prostate cancer incidence of 2.7 years (IQR: 1.1 years to 4.9 years) were included. A time-dependent multivariable analysis of spironolactone exposure following HF diagnosis found a reduced the risk of prostate cancer HR 0.55 (95% CI 0.31 - 0.98, p= 0.043).

CONCLUSION: Spironolactone exposure significantly reduced the incidence of prostate cancer amongst men with HF. These findings support the plausibility of aldosterone as a promoter of prostate cancer growth and development. Prospective clinical trials are warranted to further assess the role of spironolactone or other mineralocorticoid receptor antagonists as a means to prevent prostate cancer development or as an adjunctive measure to prostate cancer treatments.