Comparative Efficacy of Different Drugs for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Bayesian Network Meta-Analysis

Abstract

Background: Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are common in middle-aged and elderly men. The current drugs for treating this disease include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and β3-adrenoceptor agonists (B3As). However, direct comparative studies analyzing different therapies are limited; therefore, we conducted a network meta-analysis (NMA) to evaluate the efficacy of different drug regimens for treating BPH/LUTS. Methods: The PubMed, EMbase, Web of Science, and Cochrane Library databases were searched to collect randomized controlled trials (RCTs) of different drug treatments for BPH/LUTS from January 2000 to April 2021. The NMA was performed using R 4.1 software. Results: Fifty-five RCTs were included among a total of 1639 trials. ① ABs + PDE5-Is, ABs + B3As, ABs + MRAs, ABs, and PDE5-IS were superior to the placebo in improving the total International Prostate Symptom Score (IPSS), IPSS-Voiding, and IPSS-storage. ② For increasing the maximum flow rate (Qmax), ABs + PDE5-Is, ABs + MRAs, and ABs were more effective than the placebo. ③ Regarding reducing post-void residual urine (PVR), none of the six treatment plans had significant effects. Conclusion: Combination therapy showed greater efficacy than monotherapy, and ABs + PDE5-Is was the most successful treatment for improving the overall IPSS score. ABs are a primary therapeutic measure to increase Qmax, and ABs + PDE5-I may be a more suitable choice for enhancing Qmax. The combination of MRA and AB+ MRA may lead to an increase in PVR. Systematic Review Registration: [website], identifier [registration number].

Keywords: benign prostatic hyperplasia; drug treatment; lower urinary tract symptoms; network meta-analysis; randomized controlled trial.

FIGURE 1

Flow diagram of the identification process for eligible studies.

FIGURE 2

Risk of bias summary plot.

FIGURE 3

Network plots for different outcomes. (A) International Prostate Symptom Score (IPSS); (B) IPSS-storage; (C) IPSS-voiding; (D) post-void residual urine (PVR); (E) maximum flow rate (Qmax). include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and β3-adrenoceptor agonists (B3As).

FIGURE 4

Forest plots. (A) International Prostate Symptom Score (IPSS); (B) maximum flow rate (Qmax); (C) post-void residual urine (PVR). include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and β3-adrenoceptor agonists (B3As).

FIGURE 5

Surface under the cumulative ranking curve (SUCRA) plots. (A) International Prostrate Symptom Score (IPSS) SUCRA values: α1-adrenoceptor antagonists (ABs)+ phosphodiesterase five inhibitors (PDE5−Is) (99.02%), ABs+β3-adrenoceptor agonists (B3As) (67.07%), ABs + muscarinic receptor antagonists (MRAs) (66.78%), PDE5−Is (46.69%), ABs (46.47%), and MRAs (21.8%); (B) IPSS-storage SUCRA values: ABs + B3As (86.9%), ABs + MRAs (81.97%), ABs + PDE5−Is (69.9%), ABs (33.3%), and PDE5−Is (27.93%); (C) IPSS-voiding SUCRA values: ABs + PDE5−Is (98.55%), ABs + B3As (57.48%), PDE5−Is (57.37%), ABs (52.2%), and ABs + MRAs (34.31%); (D) Maximum flow rate (Qmax) SUCRA values: ABs + PDE5−Is (97.58%), ABs 68.73%), ABs + MRAs (54.82%), ABs + B3As (51.78%), MRAs (50.2%), and PDE5−Is (17.86%); (E) Post-void residual urine (PVR) SUCRA values: ABs + PDE5−Is (94.81%), ABs (85.1%), PDE5−Is (55.67%), ABs + B3As (40.75%), ABs + MRAs (15.49%), and MRAs (5.06%).

FIGURE 6

Forest plots. (A) International Prostate Symptom Score (IPSS)-storage; (B) IPSS-voiding. include α1-adrenoceptor antagonists (ABs), muscarinic receptor antagonists (MRAs), phosphodiesterase five inhibitors (PDE5-Is), and β3-adrenoceptor agonists (B3As).

FIGURE 7

Funnel-plots (A) International Prostrate Symptom Score (IPSS) (Egger’s test, p = 0.095); (B) IPSS-storage (Egger’s test, p = 0.067); (C) IPSS-voiding (Egger’s test, p = 0.103); (D) Maximum flow rate (Qmax) (Egger’s test, p = 0.104); (E) Post-void residual urine (PVR) (Egger’s test, p = 0.901). A: α1-adrenoceptor antagonists (ABs); B: phosphodiesterase five inhibitors (PDE5-Is); C: Placebo; D: muscarinic receptor antagonists (MRAs); E: ABs + B3As; F: ABs + PDE5-Is; and G: ABs + MRAs.