PhD Student UNC Chapel Hill Gillings School of Global Public Health, United States
Background: Alpha-1 blockers (AB) and 5-alpha reductase inhibitors (5-ARI) are mainstay pharmacologic treatments for benign prostatic hyperplasia (BPH). However, results of controlled experiments have suggested that blockage of alpha-1A adrenergic receptors by AB may increase the risk of adverse cardiovascular outcomes.
Objectives: To estimate the effect of AB vs. 5-ARI on the 1- year risk of (1) hospitalization for heart failure (HF), (2) major adverse cardiovascular events (MACE) (hospitalization for stroke, hospitalization for myocardial infarction [MI], or death), (3) MACE or HF hospitalization, and (4) death.
Methods: We used a 20% random sample of Medicare Fee-for-Service beneficiaries to identify men who were new-users of AB or 5-ARI between January 2007 and December 2019. Patients were required to be 66 to 90 years of age, have received a diagnosis for BPH ≤12 months prior to new-use, and continuously enrolled in Medicare Parts A, B, and D for ≥12 months prior to new-use. Follow-up began at the second prescription fill date; patients who initiated the other study drug between the 1st and 2nd fill were excluded. Patients were followed until the outcome of interest, death, or disenrollment. Cumulative incidence was calculated via Kaplan-Meier or Aalen Johansen estimators for the HF outcome, treating death as a competing event. We estimated crude and inverse probability of treatment (IPT) weighted 1- year risk ratios (RR) and risk differences (RD) that accounted for demographics, comorbidities, and frailty.
Results: We identified 168,827 new-users of AB and 26,039 new-users of 5-ARI. Patients treated with ABs had a higher prevalence of cardiovascular diseases and antihypertensive use at cohort entry. Patients were balanced on all measured covariates after IPT weighting. The 1-year risk of hospitalization for HF was 3.83% and 3.86% for new-users of ABs and 5-ARIs, respectively (aRR: 0.99 [95% CI: 0.92, 1.07]; aRD: -2.3 per 10,000 [95% CI: -32.0, 27.3]). The 1-year risk of MACE was 8.95% and 8.32% (aRR: 1.08 [95% CI: 1.02, 1.13]; aRD: 6.3 per 1,000 [95% CI: 2.1, 10.4]). The 1-year risk for the composite outcome of MACE or hospitalization for HF was 11.14% and 10.40% for new-users of ABs and 5-ARIs, respectively (aRR: 1.07 [95% CI: 1.03, 1.12]; aRD: 7.4 per 1,000 [95% CI: 2.9, 11.9]). The 1-year risks for death were 6.03% and 5.64% (aRR: 1.07 [95% CI: 1.01, 1.14]; aRD: 3.8 per 1,000 [95% CI: 0.4, 7.3]).
Conclusions: Our study found a slight increase in risk for several cardiovascular outcomes associated with AB compared to 5-ARI use. However, residual confounding by unmeasured differences in baseline cardiovascular risk factors (e.g., BMI, diabetes severity) may partly explain these results.
