(AG) Mineralocorticoid Receptor Antagonists and Prostate Cancer Risk in Patients with Heart Failure

Publication Number: 323

Background: Patients with heart failure (HF) are at elevated risks for subsequent cancer diagnoses. Mineralocorticoid receptor antagonists (MRAs), which are well-established treatments for HF, may be associated with a reduced risk for prostate cancer development.

Objectives: To investigate the association between MRA use and prostate cancer diagnosis in male patients with HF.

Methods: We conducted a population-based cohort study using the IQVIA Medical Research Data (IMRD)-UK data (formally known as THIN database). All male patients with their first HF diagnosis between 2004 and 2019 were identified using the Read Codes from the diagnostic records. The MRA use was ascertained by the first prescription records after the HF diagnosis and was classified into spironolactone and eplerenone. Patients entered the study at the first HF diagnosis and the follow-up was split into three-month intervals. Using a marginal structural model approach, time-varying confounders associated with time-varying exposure and outcome were adjusted, and pooled logistic regression models with robust variance estimator were used to estimate the hazard ratio (HR) of prostate cancer risk. We further explored the dose-response relationship of the associations by stratifying the follow-up intervals by cumulative Defined Daily Doses (cDDD) since treatment initiation.

Results: The preliminary results showed a total of 48,964 male patients with HF were included in the study; 868 developed incident prostate cancer during a median follow-up time of 3.0 years [interquartile range (IQR), 1.0-5.8 years]. MRA use was associated with a reduced risk for prostate cancer diagnosis in the study population [HR, 0.73; 95% confidence interval (CI), 0.61-0.86]; the associations were observed for both spironolactone (HR, 0.75; 95%CI, 0.63-0.89) and eplerenone (HR, 0.54; 95%CI, 0.33-0.89). The reduction of risk of MRA appeared to be dose-dependent, where the largest effect size was observed with 600 or more cDDDs of MRA use (HR, 0.48; 95% CI, 0.31-0.76).

Conclusions: MRA use was associated with a significantly lower risk of prostate cancer diagnosis in male patients with HF. Further studies are warranted to explore the potentially different mechanisms between spironolactone and eplerenone and to determine their roles in prostate cancer chemoprevention.