Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia
Authors: Pattanaik Smita , Mavuduru Ravimohan S. , Panda Arabind , Mathew Joseph L. , Agarwal Mayank M. , Hwang Eu Chang , Lyon Jenifer A. , Singh Shrawan K. , Mandal Arup K. 
Published: January 2019

ObjectivesTo assess the effects of phosphodiesterase inhibitors (PDEI) compared to placebo and other standard of care drugs i.e alpha blockers (AB) and 5‐alpha reductase inhibitors (5‐ARI) in men with LUTS consistent with benign prostatic hyperplasia (BPH).MethodsWe conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). Citation tracking and hand‐searching of abstracts and conference proceedings was done. We also attempted to contact the study authors in case additional information was needed. Randomised controlled trials (RCT) comparing PDEI versus placebo, AB, or 5‐ARI used for at least four weeks in men with BPH‐LUTS were included. Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS‐total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AE). We used GRADE to rate the quality of evidence. We considered short‐term (up to 12 weeks) and long‐term (12 weeks or longer) results separately.ResultsWe included a total of 16 randomised trials in this review.Primary outcomes: PDEI versus placebo: PDEI may result in a small improvement in IPSS‐total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low‐quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low‐quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low‐quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI versus AB: PDEI and AB probably provide similar improvement in IPSS‐total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate‐quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low‐quality evidence) and AE (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low‐quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks.PDEI and AB versus AB : The combination of PDEI and AB may provide a small improvement in IPSS‐total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low‐quality evidence) compared to AB alone. We found no evidence for BPHII scores. AE may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate‐quality evidence). This corresponds to 235 more AE per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks.PDEI and AB versus PDEI alone: The combination of PDEI and AB may provide a small improvement in IPSS‐total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low‐quality evidence) compared to PDEI alone. We found no data on BPHII or AE. Study results were limited to a treatment duration of four weeks.PDEI and 5‐ARI versus 5‐ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5‐ARI probably results in a small improvement in IPSS‐total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate‐quality evidence) compared to 5‐ARI alone. We found no evidence on BPHII scores or AE. In the long term (13 to 26 weeks), the combination of PDEI and 5‐ARI likely results in a small reduction in IPSS‐total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate‐quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AE (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low‐quality evidence). This corresponds to 19 more AE per 1000 participants (95% CI 43 fewer to 98 more per 1000). We found no trials comparing other combinations of treatments or comparing different PDEI for BPH‐LUTS.ConclusionsCompared to placebo, PDEI likely leads to a small reduction in IPSS‐total and BPHII sores, with a possible increase in AE. There may be no differences between PDEI and AB with regards to improvement in IPSS‐total, BPHII, and incidence of AE. There appears to be no added benefit of PDEI combined with AB compared to PDEI or AB or PDEI combined with 5‐ARI compared to ARI with regards to urinary symptoms. Most evidence was limited to short‐term treatment up to 12 weeks and of moderate or low certainty.