Cardiovascular safety of 5α-reductase inhibitors in people with benign prostatic hyperplasia and type 2 diabetes: a propensity score-matched analysis

AIMS: 5α-Reductase inhibitors are prescribed for the treatment of benign prostatic hyperplasia (BPH) and their use is associated with increased risk of incident type 2 diabetes. This study assessed the long-term cardiovascular safety of 5α-reductase inhibitors in comparison with tamsulosin in people with co-existing BPH and type 2 diabetes. METHODS AND RESULTS: We performed a retrospective, population-based cohort study using Scottish Diabetes Research Network National Diabetes Dataset (SDRN-NDS) and IQVIA Medical Research Data (IMRD-UK). BPH patients ≥40 years with recorded type 2 diabetes mellitus and ≥2 prescriptions of 5α-reductase inhibitors or tamsulosin (2006-2021) were included. After 1:2 variable ratio propensity score matching, cause-specific Cox proportional-hazard models were used to compute the hazard ratio (HR) of incident major adverse cardiovascular events (MACE). A total of 11 969 patients were included in SDRN-NDS and 16 492 in IMRD-UK, with median follow-up durations of 3.8 (IQR: 1.7-6.8) and 4.8 (2.0-8.3) years, respectively. In SDRN-NDS, the HR of MACE in patients receiving 5α-reductase inhibitors relative to tamsulosin was 1.15 (95% CI 1.03-1.30, P = 0.007), driven by increased risk of myocardial infarction (MI) (HR 1.20, 1.03-1.40, P = 0.022). This was replicated in IMRD-UK, where HR was 1.26 (1.07-1.47, P = 0.008) for MACE and 1.33 (1.10-1.60, P = 0.005) for MI. We did not observe any increased risks in stroke, cardiovascular death, microvascular complications of diabetes, or faster progression to insulin-based therapies. CONCLUSION: Our retrospective data from two large cohorts suggest that the risk of MACE may be increased among patients with type 2 diabetes taking 5α-reductase inhibitors, potentially driven by increased risk of MI. This supports careful monitoring of macrovascular outcomes when prescribing 5α-reductase inhibitors in this population.