Silodosin vs Other Alpha Blockers Including Tamsulosin for LUTS/BPH: A Cochrane Review
Introduction
Alpha-blockers are standard therapy for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), with tamsulosin being a well-established agent. Silodosin, a newer and more selective alpha-1A blocker, was compared to tamsulosin in early trials, showing similar efficacy but with a higher incidence of abnormal ejaculation and comparable cardiovascular adverse events.
Aim
To compare the efficacy and safety of silodosin versus tamsulosin and other alpha blockers in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).
Patient Profile
- N=4,295 men adult men (≥40 years) with LUTS due to BPH
Methods
- Systematic review and meta-analysis
- 19 randomized controlled trials (RCTs), parallel-group and cross-over RCTs
Interventions:
- Experimental: Silodosin (8 mg/day standard dose; 4 mg twice daily in some trials). One study prescribed 4 mg once daily whereas two titrated the drug dose (4 mg followed by 8 mg)
- Comparators: Placebo or other oral alpha-blockers (tamsulosin, naftopidil, alfuzosin)
- All treatments were given as monotherapy
- Duration of intervention was 12 weeks in 11 studies
Study endpoints
Primary Outcomes: Urologic symptom scores (e.g., IPSS), quality of life (QoL), treatment withdrawal for any reason
Secondary Outcomes: Withdrawal due to adverse events, acute urinary retention (AUR), surgical intervention for LUTS/BPH, cardiovascular adverse events, sexual adverse events
Results
- Compared to placebo, silodosin may reduce urinary symptom scores but showed little improvement in quality of life, did not increase overall treatment withdrawals, and had uncertain cardiovascular effects; however, it likely caused a significant rise in sexual adverse events
- Compared to tamsulosin, silodosin offered similar symptom relief and quality of life, with uncertain impact on treatment withdrawals and cardiovascular events, but substantially increased sexual side effects
- Compared to naftopidil, silodosin demonstrated comparable efficacy and safety for most outcomes, except for a marked increase in sexual adverse events.
- Compared to alfuzosin, silodosin may or may not worsen symptom scores, showed minimal effect on quality of life, no difference in treatment withdrawals, and likely increased sexual adverse events significantly, with no clear cardiovascular benefit.
Table 1: Comparative Outcomes of Silodosin vs Placebo and Other Alpha-Blockers in BPH
|
Comparison |
Urologic Symptom Scores (IPSS) |
Quality of Life |
Treatment Withdrawal |
Cardiovascular Events |
Sexual Adverse Events |
|
Silodosin vs Placebo |
n=1743 (3 RCTs), low evidence |
n=820 (2 RCTs), Moderate evidence |
n=1703 (3 RCTs), low evidence |
N=1967 (4 RCTs), very low evidence |
N=1967 (4 RCTs), moderate evidence |
|
Improves (MD = -2.65, 95% CI: -3.23 to -2.08) |
Little/no improvement (MD = -0.42, 95% CI: -0.71 to -0.13) |
RR = 1.08 (95% CI: 0.70 to 1.66) |
RR = 1.28 (95% CI: 0.67 to 2.45) |
Significantly higher (RR = 26.07, 95% CI: 12.36 to 54.97) |
|
|
Silodosin vs Tamsulosin |
n= 1708 (10 RCTs), low evidence |
n=1707 (10 RCTs), low evidence |
n=1573 (10 RCTs), very low evidence |
n=1955 (11 RCTs), low evidence |
n= 1849 (10 RCTs), moderate evidence |
|
Similar (MD = -0.04, 95% CI: -1.31 to 1.24) |
Similar (MD = -0.15, 95% CI: -0.53 to 0.22) |
RR = 1.02 (95% CI: 0.62 to 1.69) |
RR = 0.77 (95% CI: 0.53 to 1.12) |
Higher (RR = 6.05, 95% CI: 3.55 to 10.31) |
|
|
Silodosin vs Naftopidil |
n=652 (5 RCTs), low evidence |
n= 652 (5 RCTs), low evidence |
n= 659 (4 RCTs), low evidence |
n= 808 (5 RCTs), low evidence |
n= 405 (4 RCTs), moderate evidence |
|
Similar (MD = -0.85, 95% CI: -2.57 to 0.87) |
Similar (MD = -0.17, 95% CI: -0.60 to 0.27) |
RR = 1.25 (95% CI: 0.81 to 1.93) |
RR = 1.02 (95% CI: 0.41 to 2.56) |
Higher (RR = 5.93, 95% CI: 2.16 to 16.29) |
|
|
Silodosin vs Alfuzosin |
n= 60 (1 RCT), low evidence |
n=60 (1 RCT), moderate evidence |
n= 60 (1 RCT), low evidence |
n= 60 (1 RCT), low evidence |
n= 95 (1 RCT), moderate evidence |
|
Possibly worse (MD = +3.83, 95% CI: 0.12 to 7.54) |
No benefit (MD = +0.14, 95% CI: -0.46 to 0.74) |
Not estimable |
RR = 0.67 (95% CI: 0.36 to 1.24) |
Much higher (RR = 37.21, 95% CI: 5.32 to 260.07) |
Conclusion
- Silodosin may significantly reduce urologic symptom scores in many men with BPH compared to placebo
- Its efficacy was comparable to other alpha-blockers such as tamsulosin, naftopidil, and alfuzosin. It was associated with a higher incidence of sexual adverse effects, particularly abnormal ejaculation, which may be a concern for sexually active men
- Longer-term trials for long-term efficacy and safety are warranted
Reference
Cochrane Database Syst Rev. 2017 Nov 22;11(11):CD012615
