(247) Comparative Effectiveness of 5-Alpha-Reductase Inhibitors Vs. Alpha-Blockers on The Long-Term Risk of Progression of Benign Prostatic Hyperplasia

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 921

Presenting Author(s)

Maria B. Bengtsen
– MD, PhD student, Department of Clinical Epidemiology, Aarhus University, Aarhus University, Aarhus N, Denmark

Co-Author(s)

Uffe Heide-Jørgensen
– Aarhus N, Midtjylland, Denmark
Michael Borre
– Department of Urology, Aarhus University Hospital, Denmark
Mette Norgaard, MD, PhD
– Professor, MD, PhD, Department of Clinical Epidemiology, Aarhus University, Aarhus N, Midtjylland, Denmark

Background: Clinical trials have demonstrated that 5-alpha-reductase inhibitors (5-ARIs), but not alpha-blockers, reduce the risk of benign prostatic hyperplasia (BPH)-related surgery and acute urinary retention (AUR). However, a large gap exists between treatment duration in clinical trials and real-life situations.

Objectives: To assess the long-term 15-year effectiveness of treatment with 5-ARIs versus alpha-blockers on the risk of progression to BPH related surgery and AUR.

Methods: Analyses for this study were conducted in May 2022. Using data from National Danish Health registries, we identified all new-users of 5-ARI or alpha-blocker monotherapy in Denmark, 1997-2017. We defined an index date 180 days after date of first prescription, and included men who redeemed at least two prescriptions of either 5-ARI or alpha-blocker monotherapy before index date. We used multiple imputation to replace missing prostate specific antigen values. We followed patients from index date until BPH surgery/AUR, death, migration or end of follow-up, and compared the risk of progression in the two treatment groups, using standardized mortality ratio weighting (SMRW) adjusted Cox regression to estimate the hazard ratio (HR) and cumulative incidence function, treating death as a competing risk. We computed the risk of overall progression - defined as progression to BPH surgery or AUR - and the risk of progression to BPH surgery and AUR separately. Additionally, we estimated the relative risk reduction (RRR), the absolute risk reduction (ARR) and number needed to treat (NNT).

Results: We included 126,423 men who received 5-ARIs (n=22,099) versus alpha-blockers (n=104,324).
In the SMRW-adjusted Cox regression analysis, treatment with 5-ARI versus alpha-blocker was associated with a reduced risk of overall progression (HR=0.77 (0.74-0.81)), BPH surgery (HR=0.77 (0.72-0.82)) and AUR (HR=0.74 (0.69-0.79)). The SMRW-adjusted 15-year risk of overall progression was 25.6% (24.8%-26.4%) in the 5-ARI group versus 31.1% (30.6%-31.5%) in the alpha-blocker group (RRR= 17.7%, ARR 5.5%, and NNT 18). For BPH-related surgery, the SMRW-adjusted 15-year risk was 15.2% (14.5%-15.8%) in the 5-ARI group versus 18.9% (18.5%-19.3%) in the alpha-blocker group (RRR=19.6%, ARR=3.7% and NNT=27). The SMRW-adjusted 15-year risk of AUR in men receiving 5-ARI versus alpha-blocker monotherapy was 13.3% (12.7%-13.9%) versus 16.8% (16.5%-17.2%), respectively (RRR=20.8%, ARR=3.5%, NNT=29).

Conclusions: Treatment with 5-ARI versus alpha-blocker monotherapy was associated with a reduced 15-year risk of BPH-related surgery and AUR. Still, with an ARR ranging from ranging from 3.5%-5.5%, individualized treatment with careful consideration of side effects versus beneficial effects is essential.