Cardiovascular Outcomes with α1 Adrenergic Receptor Antagonists vs 5α-Reductase Inhibitors

Background-Blockers (ABs) are the most commonly prescribed medications for benign prostatic hyperplasia (BPH), a highly prevalent condition. Although the ALLHAT raised concerns about cardiovascular (CV) safety of nonselective ABs for the treatment of hypertension, the comparative CV risk profile of selective 1A-adrenergic receptor (1A-AR) antagonists for BPH remains unclear. MethodsWe conducted a retrospective cohort study using the TriNetX federated research network (158 million patients across 113 healthcare organizations). Males aged 55 to 90 years with BPH who initiated ABs or 5-ARIs between October 1, 2015, and database lock were included. Three propensity score-matched analyses were conducted: (1) selective 1A-AR antagonists versus 5-ARIs (n=48,096 per group); (2) nonselective ABs versus 5-ARIs (n=33,232 per group); and (3) 1A-selective versus nonselective ABs (n=54,872 per group). Exposures were new use of selective 1A-AR antagonists, nonselective ABs, or 5-ARIs with evidence of adherence. Main outcomes and measures were heart failure (HF) hospitalization, acute MI, stroke, any hospitalization, major adverse CV events (MACE), and composite MACE plus HF at 1, 3, and 5 years. ResultsIn the 1A-selective AB versus 5-ARI analysis, 1A-selective ABs were associated with increased risk at 1 year of HF (hazard ratio [HR], 1.48 [95% CI, 1.39-1.57]), MI (HR, 1.41 [95% CI, 1.28-1.54]), and stroke (HR, 1.36 [95% CI, 1.22-1.50]). Similar patterns were observed for nonselective ABs versus 5-ARIs: HF (HR, 1.46), MI (HR, 1.29), stroke (HR, 1.32). At 5 years, CV risks remained elevated: HF (HR, 1.50 for selective ABs; HR, 1.52 for nonselective ABs), MI (HR, 1.41; HR, 1.30), and stroke (HR, 1.37; HR, 1.29). Head-to-head comparison of selective versus nonselective ABs showed similar CV outcomes (HF HR, 1.10 at 1 year). ConclusionsBoth 1A-selective and nonselective ABs were associated with increased CV event risk compared with 5-ARIs that persisted through 5 years of follow-up. These findings, which were robust across sensitivity analyses and specific to clinically important CV endpoints, may inform shared decision-making for BPH pharmacotherapy.