The efficacy and safety of combined therapy with α-blockers and anticholinergics for men with benign prostatic hyperplasia: a meta-analysis

Abstract

Purpose: We performed a meta-analysis to compare treatment with α-blockers and anticholinergics (ie combination therapy) to α-blocker monotherapy to clarify the efficacy and safety of this treatment approach among men with storage urinary symptoms related to benign prostatic hyperplasia.

Materials and methods: We searched for trials of men with benign prostatic hyperplasia/lower urinary tract symptoms that were randomized to combination treatment or α-blockers alone. We pooled data from 7 placebo controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (storage subscores) and urinary frequency. We also assessed post-void residual volume, maximal flow rate and the incidence of urinary retention. Data were pooled using random effects models for continuous outcomes and the Peto method to generate odds ratios for acute urinary retention.

Results: Combination therapy had a significantly greater reduction in International Prostate Symptom Score storage subscores (Δ -0.73, 95% CI -1.09 - -0.37) and voiding frequency (Δ -0.69 voids, 95% CI -0.97 - -0.41). There was also a greater reduction in maximal urinary flow rate (Δ -0.59 ml per second, 95% CI -1.04 - -0.14) and increase in post-void residual urine volume (Δ 11.60 ml, 95% CI 8.50-14.70) with combination therapy. The number needed to treat with combination therapy to cause 1 acute urinary retention episode was 101 (95% CI 60-267).

Conclusions: Combination treatment with α-blockers and anticholinergics significantly improved storage voiding parameters compared to men treated with α-blocker therapy alone. This treatment approach is safe with a minimal risk of increased post-void residual urine volume, decreased maximal urinary flow rate or acute urinary retention.

Keywords: AUR; BPH; CO; ER; I-PSS; International Prostate Symptom Score; LUTS; PVR; Qmax; RCT; WMD; acute urinary retention; adrenergic alpha-antagonists; benign prostatic hyperplasia; cholinergic antagonists; combination therapy; combined modality therapy; extended release; lower urinary tract symptoms; maximal urinary flow rate; meta-analysis; post-void residual urine volume; prostatic hyperplasia; randomized clinical trial; weighted mean difference.

Figure 1

Study selection process for trials included in meta-analysis

Figure 2

Forest plots of primary outcomes from pooled analysis, stratified by prior use of α-blockers. Figure is divided between 2 primary outcomes of interest for meta-analysis. Mean difference is difference between treatment effect of combination therapy compared to α-blocker monotherapy. Sizes of data markers are proportional to weight of each study in analysis. Horizontal bars represent 95% CI for each study. X axis represents magnitude of change of each outcome of interest. Data to left of black vertical line represent greater reduction of each outcome with combination therapy and data to right represent greater increase with combination therapy. White diamonds represent pooled effect sizes for each subgroup and overall, which extend to 95% CI of pooled data. Gray broken vertical line represents value of overall pooled effect size. P values correspond to test of significance for pooled data. I2 values represent heterogeneity of each analysis.

Figure 3

Forest plots of PVR and Qmax outcomes, stratified by prior use of α-blockers, divided between 2 secondary outcomes of interest for meta-analysis. Mean difference is difference between treatment effect of combination therapy compared to α-blocker monotherapy. Sizes of data markers are proportional to weight of each study in analysis. Horizontal bars represent 95% CI for each study. X axis represents magnitude of change of each outcome of interest. Data to left of black vertical line represent greater reduction of each outcome with combination therapy and data to right represent greater increase with combination therapy. White diamonds represent pooled effect sizes for each subgroup and overall, which extend to 95% CI of pooled data. Gray broken vertical line represents value of overall pooled effect size. P values correspond to test of significance for pooled data. I2 values represent heterogeneity of each analysis.

Figure 4

Forest plots of odds ratios for acute urinary retention and urethral catheterization, divided between 2 outcomes related to AUR in meta-analysis. Mean difference is difference between treatment effect of combination therapy compared to α-blocker monotherapy. Sizes of data markers are proportional to weight of each study in analysis. Horizontal bars represent 95% CI for each study. X axis represents magnitude of change of each outcome of interest. Data to left of black vertical line represent decreased odds of each outcome with combination therapy and data to right represent increased odds of each outcome with combination therapy. White diamonds represent pooled odds ratios, which extend to 95% CI of pooled data. Gray vertical line represents value of overall pooled odds ratios. P values correspond to test of significance for pooled data. I2 values represent heterogeneity of each analysis.