A Meta-Analysis of Long-Versus Short-Acting Phosphodiesterase 5 Inhibitors: Comparing Combination Use With alpha-Blockers and alpha-Blocker Monotherapy for Lower Urinary Tract Symptoms and Erectile Dysfunction

Abstract

Purpose: Combination therapy with an alpha-1-adrenergic blocker and phosphodiesterase type 5 inhibitors (PDE5Is) has shown improvements in lower urinary tract symptoms (LUTS) with negligible side effects. Nonetheless, decisive advantages in symptom improvement were insufficient, and there were no clinical differences between long-or short-acting PDE5Is in combination with combination medication. Methods: To review the studies on alpha-1-adrenergic blocker monotherapy and combination therapy with long vs. short-acting PDE5Is in their use in LUTS and erectile dysfunction (ED). A search of the MEDLINE, Embase, Cochrane Library, and Korea-Med databases was conducted from 2000 to 2014 using combinations of the relevant terms. Among the 323 relevant references discovered, 10 were selected for meta-analysis. The data showed that 616 men received combination therapy (PDE5Is with alpha-1-adrenergic blockers) or alpha-1-adrenergic blocker monotherapy. Results: Meta-analysis of the combination therapy showed it was more effective than alpha-blockers in improving symptoms, with a mean International Prostrate Symptom Score change difference of -1.93 while those of the long-vs. short-acting PDE5I were -2.12 vs. -1.70. Compared to maximum flow rate (Qmax) value with monotherapy, the Qmax increased more with the combination therapy (mean difference of 0.71) while change values were 0.14 and 1.13 for the long-and short-acting PDE5Is, respectively. Residual urine decreased more with the combination therapy than it did with alpha-1-adrenergic blocker monotherapy with a mean difference of -7.09 while the mean residual urine change values for long-vs. short-acting PDE5Is were -18.83 vs. -5.93. The International Index of Erectile Function value increased by 3.99, 2.85, and 4.85 following combination therapy, and therapy with long-and short-acting PDE5Is. Conclusions: Our meta-analysis suggests that PDE5Is can significantly improve LUTS in men with benign prostatic hyperplasia/ED. Furthermore, combination PDE5I and alpha-1-adrenergic blocker could be a more effective treatment than alpha-1-adrenergic blocker monotherapy, and the differences between long and short-acting agents were minimal.