Cardiovascular Outcomes of Alpha-Blockers Versus 5-Alpha Reductase Inhibitors Among Patients with Benign Prostatic Hyperplasia

Importance Alpha-blockers (AB) are widely prescribed for treatment of benign prostatic hyperplasia (BPH). However, the cardiovascular safety profile of these medications among patients with BPH is not well understood. Objective To compare the safety of ABs versus 5-alpha reductase inhibitors (5ARIs) for risk of adverse cardiovascular outcomes. Design We conducted an active comparator, new user, cohort study using insurance claims data from 2007-2019. Setting This study used data from a 20% random sample of Medicare (U.S.) beneficiaries. Participants Men between 66 and 90 years of age were indexed into the cohort at new use of an AB or 5ARI. We required 12 months of continuous enrollment and ≥1 diagnosis code for BPH within 12 months prior to initiation. Exposures Exposure was defined by a qualifying prescription fill for either an AB or 5ARI after at least 12 months without a prescription for these drug classes. Main Outcomes and Measures Follow-up began at a qualified refill for the study drug. The primary study outcomes were (1) hospitalization for heart failure (HF); (2) composite major adverse cardiovascular events (MACE) (hospitalization for stroke, myocardial infarction, or death); (3) composite MACE or hospitalization for HF; and (4) death. We estimated inverse probability of treatment and censoring weighted 1-year risks, risk ratios (RRs), and risk differences (RDs) for each outcome. Results We identified 163,846 and 26,040 initiators of ABs and 5ARIs, respectively. In our fully adjusted analyses, we found ABs, compared to 5ARIs, were associated with an increased 1-year risk of MACE (RR=1.08 [1.02, 1.13], RD=6.26 per 1,000 [2.15, 10.37]), composite MACE and HF (RR=1.07 [1.03, 1.12], RD=7.40 per 1,000 [2.88, 11.93]), and death (RR=1.07 [1.01, 1.14], RD=3.85 per 1,000 [0.40, 7.29]). We did not find a difference in risk for HF alone (RR=0.99 [0.92, 1.07], RD=-2.33 per 10,000 [-31.97, 27.31]). Conclusions and Relevance These results provide real-world evidence that ABs may be associated with an increased risk of adverse cardiovascular outcomes, though residual confounding may explain these findings. If replicated with detailed confounder data, these results could have important public health implications given the widespread use of these medications. Three Key Points Question What is the comparative risk of alpha-blockers versus 5-alpha reductase inhibitors for adverse cardiovascular outcomes among patients with benign prostatic hyperplasia? Findings We found that use of alpha-blockers was associated with a small increase in risk for multiple adverse cardiovascular outcomes compared to 5-alpha reductase inhibitors, among patients with benign prostatic hyperplasia. These results could be explained by unmeasured variables (e.g., blood pressure or body mass index). Meaning First-line use of alpha-blockers for BPH may result in a small increase in risk of adverse cardiovascular outcomes including death. Widescale use of alpha-blockers (>5 million prescriptions/year) could amplify this risk.