madman
Super Moderator
Purpose: This study aimed to compare the efficacy and safety of combination therapy consisting of a-blockers and different phosphodiesterase type 5 inhibitors for lower urinary tract symptoms (LUTS) by performing a network meta-analysis.
Method: Relevant articles were retrieved from the Cochrane Library, PubMed, and EMBASE databases. Bayesian network meta-analyses were performed with a random-effect model to compare the efficacy and safety of combination therapy with a-blockers and phosphodiesterase-5 inhibitors for LUTS. The odds ratio (OR), mean difference (MD), and the surface under the cumulative ranking curve (SUCRA) were calculated with the GeMTC R package.
Results: Twenty randomized trials with 4131 patients were included in this network meta-analysis. Based on the SUCRA values, vardenafil (10mg) combined with a-blockers ranked first, first, and sixth; sildenafil (25mg) combined with a-blockers ranked second, third and first; and tadalafil (20mg) combined with a-blockers ranked third, second and fourth in IPSS, post-void residual, and maximum flow rate, respectively.
Conclusions: Combination therapy with a-blockers and phosphodiesterase-5 inhibitors was effective and well-tolerated for LUTS. For men who prioritize high efficacy, vardenafil (10mg) combined with a-blockers seems to be the treatment of choice. For men wishing to optimize minimally invasive treatment, sildenafil (25mg) and tadalafil (20mg) combined with a-blockers appear to have a possible advantage in terms of avoiding adverse effects.
1. Introduction
Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are prevalent conditions that have negative impacts on quality of life and self-confidence.[1,2] The prevalence of LUTS in men aged over 50 years old has been reported to be more than 50%.[3] Based on the pathophysiological relationships between BPH-LUTS and ED, several studies have confirmed that both diseases often coexist and have a growing prevalence with age.[4,5]
The European Association of Urology guidelines proposed a-adrenergic blockers as the first-line therapy for the treatment of BPH-LUTS. Nevertheless, phosphodiesterase-5 inhibitors (PDE5Is), including sildenafil, vardenafil, and tadalafil, are currently present in the first line of effective pharmacotherapy options for patients with ED. Recently, several studies have suggested that treatment with PDE5Is cures BPH-LUTS because BPH-LUTS and ED share a similar pathophysiological pathway. Although recent studies have demonstrated that PDE5Is can effectively treat LUTS, the administration of PDE5Is and treatment-related adverse events remain unclear.[6,7]
Oral PDE5Is was first approved for the treatment of ED in 1998. The mechanism of action involves the PDE5I-induced increase in the level of the second messenger cyclic guanosine monophosphate, which promotes smooth muscle relaxation and induces penile erection. In theory, PDE5Is can increase the level of nitric oxide in smooth muscle, which in turn relaxes the smooth muscle of urinary organs (such as the bladder neck, and prostate) and ultimately relieves the symptoms of LUTS associated with BPH.
Studies have shown that combination therapy with PDE5Is and a-blockers provided better outcomes than a-adrenergic blocker monotherapy. In our analysis, studies related to combination therapy consisting of a-blockers and different PDE5Is were identified and systemically evaluated, with the aim of providing a basis for the future clinical treatment of LUTS.
4. Discussion
Studies have shown that PDE5Is combined with a-blockers are superior to a-blocker monotherapy with regard to improving the symptoms of LUTS, and the adverse events of the combined treatment are not clinically important. A previous meta-analysis concluded that combination therapy with a-blockers and PDE5Is can significantly improve LUTS when compared with monotherapy, especially having an advantage in IPSS.[7] In the largest study to date, Zhang et al found that compared with monotherapy, combination therapy with a-blockers and PDE5Is is efficacious and well-tolerated in the treatment of LUTS and ED.[14] In this network meta-analysis, we systematically reviewed the efficacy and safety of monotherapy with either a-blockers or PDE5Is and the combination therapy of a-blockers plus PDE5I. There were 2 major findings in our study:
(1) combination therapy with an a-blocker plus a PDE5I was significantly more effective than a-blockers monotherapy at improving LUTS.
(2) Based on the network meta-analysis and SUCRA analysis, vardenafil (10mg) combined with a-blockers, sildenafil (25 mg) combined with a-blockers, and tadalafil (20mg) combined with a-blockers appear to be better choices than monotherapies with either a-blockers or PDE5Is and other combination therapies of a-blockers plus PDE5Is in terms of efficacy.
Previous NMAs[29,30] comparing phosphodiesterase type 5 inhibitors combined with tamsulosin among the general population suggested that sildenafil combined with tamsulosin is superior to other administrations. In our study, however, sildenafil (25mg) combined with a-blockers is not proven to be superior to other administrations.
6. Conclusions
In conclusion, combination therapy with a-blockers and PDE5Is was significantly more effective than a-blocker monotherapy at improving LUST. Among the combinations, vardenafil (10mg) combined with a-blockers, sildenafil (25mg) combined with a-blockers, and tadalafil (20mg) combined with a-blockers appear to be better choices than monotherapies with either a-blockers or PDE5Is and other combination therapies of a-blockers plus PDE5Is in terms of efficacy. However, our present results need to be verified with more high-quality studies with comprehensive data.
Method: Relevant articles were retrieved from the Cochrane Library, PubMed, and EMBASE databases. Bayesian network meta-analyses were performed with a random-effect model to compare the efficacy and safety of combination therapy with a-blockers and phosphodiesterase-5 inhibitors for LUTS. The odds ratio (OR), mean difference (MD), and the surface under the cumulative ranking curve (SUCRA) were calculated with the GeMTC R package.
Results: Twenty randomized trials with 4131 patients were included in this network meta-analysis. Based on the SUCRA values, vardenafil (10mg) combined with a-blockers ranked first, first, and sixth; sildenafil (25mg) combined with a-blockers ranked second, third and first; and tadalafil (20mg) combined with a-blockers ranked third, second and fourth in IPSS, post-void residual, and maximum flow rate, respectively.
Conclusions: Combination therapy with a-blockers and phosphodiesterase-5 inhibitors was effective and well-tolerated for LUTS. For men who prioritize high efficacy, vardenafil (10mg) combined with a-blockers seems to be the treatment of choice. For men wishing to optimize minimally invasive treatment, sildenafil (25mg) and tadalafil (20mg) combined with a-blockers appear to have a possible advantage in terms of avoiding adverse effects.
1. Introduction
Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are prevalent conditions that have negative impacts on quality of life and self-confidence.[1,2] The prevalence of LUTS in men aged over 50 years old has been reported to be more than 50%.[3] Based on the pathophysiological relationships between BPH-LUTS and ED, several studies have confirmed that both diseases often coexist and have a growing prevalence with age.[4,5]
The European Association of Urology guidelines proposed a-adrenergic blockers as the first-line therapy for the treatment of BPH-LUTS. Nevertheless, phosphodiesterase-5 inhibitors (PDE5Is), including sildenafil, vardenafil, and tadalafil, are currently present in the first line of effective pharmacotherapy options for patients with ED. Recently, several studies have suggested that treatment with PDE5Is cures BPH-LUTS because BPH-LUTS and ED share a similar pathophysiological pathway. Although recent studies have demonstrated that PDE5Is can effectively treat LUTS, the administration of PDE5Is and treatment-related adverse events remain unclear.[6,7]
Oral PDE5Is was first approved for the treatment of ED in 1998. The mechanism of action involves the PDE5I-induced increase in the level of the second messenger cyclic guanosine monophosphate, which promotes smooth muscle relaxation and induces penile erection. In theory, PDE5Is can increase the level of nitric oxide in smooth muscle, which in turn relaxes the smooth muscle of urinary organs (such as the bladder neck, and prostate) and ultimately relieves the symptoms of LUTS associated with BPH.
Studies have shown that combination therapy with PDE5Is and a-blockers provided better outcomes than a-adrenergic blocker monotherapy. In our analysis, studies related to combination therapy consisting of a-blockers and different PDE5Is were identified and systemically evaluated, with the aim of providing a basis for the future clinical treatment of LUTS.
4. Discussion
Studies have shown that PDE5Is combined with a-blockers are superior to a-blocker monotherapy with regard to improving the symptoms of LUTS, and the adverse events of the combined treatment are not clinically important. A previous meta-analysis concluded that combination therapy with a-blockers and PDE5Is can significantly improve LUTS when compared with monotherapy, especially having an advantage in IPSS.[7] In the largest study to date, Zhang et al found that compared with monotherapy, combination therapy with a-blockers and PDE5Is is efficacious and well-tolerated in the treatment of LUTS and ED.[14] In this network meta-analysis, we systematically reviewed the efficacy and safety of monotherapy with either a-blockers or PDE5Is and the combination therapy of a-blockers plus PDE5I. There were 2 major findings in our study:
(1) combination therapy with an a-blocker plus a PDE5I was significantly more effective than a-blockers monotherapy at improving LUTS.
(2) Based on the network meta-analysis and SUCRA analysis, vardenafil (10mg) combined with a-blockers, sildenafil (25 mg) combined with a-blockers, and tadalafil (20mg) combined with a-blockers appear to be better choices than monotherapies with either a-blockers or PDE5Is and other combination therapies of a-blockers plus PDE5Is in terms of efficacy.
Previous NMAs[29,30] comparing phosphodiesterase type 5 inhibitors combined with tamsulosin among the general population suggested that sildenafil combined with tamsulosin is superior to other administrations. In our study, however, sildenafil (25mg) combined with a-blockers is not proven to be superior to other administrations.
6. Conclusions
In conclusion, combination therapy with a-blockers and PDE5Is was significantly more effective than a-blocker monotherapy at improving LUST. Among the combinations, vardenafil (10mg) combined with a-blockers, sildenafil (25mg) combined with a-blockers, and tadalafil (20mg) combined with a-blockers appear to be better choices than monotherapies with either a-blockers or PDE5Is and other combination therapies of a-blockers plus PDE5Is in terms of efficacy. However, our present results need to be verified with more high-quality studies with comprehensive data.
