Phosphodiesterase inhibitors for treatment of voiding dysfunction: An overview of experimental and clinical evidence

Table 2 Randomized clinical trials and meta-analyses with strong evidence for the use of phosphodiesterase inhibitors in patients with lower urinary tract symptoms due to benign prostatic obstruction

Ref.	Design of study	Placebo run-in	Participant/inclusion criteria	End point	Major conclusion
Sairam et al[11]	Not RCT	No	112 male patients All taking sildenafil Inclusion criteria was presence ED	Assess relationship between ED and LUTS; if sildenafil influences LUTS in patients with ED	No relation between ED score and LUTS before treat ED Sildenafil improves ED and LUTS
McVary et al[14]	Open-label, randomized, double-blind, placebo-controlled	No	369 patients were randomized to sildenafil 100 mg (n = 189) or placebo (n = 180) during 12 wk/Men with ED and LUTS	Change IPSS, QoL,BPHII, Qmax, SEAR, and EDITS	Sildenafil improve IIEF, IPSS, BPHII, IPSS QoL and SEAR score Qmax not altered
McVary et al[15]	Randomized, double-blind, placebo-controlled	Yes	281 men randomized to tadalafil 5 mg daily, followed by dose escalation to 20 mg/Men aged 45 yr or higher and IPSS > 12	Change IPSS, QoL, BPHII, Qmax, and IIEF	Tadalafil improve IPSS, QoL, BPHII, and IIEF Qmax not altered
Stief et al[16]	Randomized, double-blind, placebo-controlled	No	222 men were randomized to vardenafil 10 mg twice daily or placebo/age 45-64 yr, IPSS ≥ 12, with or without ED	Change in IPSS, Qmac, PVR, and IIEF	Vardenafil improve IPSS, IIEF, and QoL Qmax and PVR not altered
Roehrborn et al[17]	Randomized, double-blind, placebo-controlled	Yes	1058 men were randomized to receive daily tadalafil 2.5, 5, 10 or 20 mg/age greater than 45 yr, IPSS ≥ 12, and Qmax between 4-15 mL/s	Change in IPSS, IIEF, QoL, BPHII, GAQ, and Qmax	Tadalafil improve IPSS and GAQ in all doses But, dose higher than 5 mg had minimal improvement with higher side effects Qmax not altered
Porst et al[20]	Meta-analysis		1026 men, tadalafil (n = 505) compared to placebo (n = 521). Data pooled from four multinational study/age ≥ 45 yr, presence of LUTS/BPO	Change in IPSS, QoL, BPHII, and IIEF	Tadalafil improve IPSS, QoL, BPHII, and IIEF compared with placebo
Gacci et al[18]	Meta-analysis		Twelve studies, been seven studies (n = 3214) comparing PDEi vs placebo, and five (n = 216) on the combination of PDEi with ∝-blockers vs∝-blockers alone/Men with LUTS/BPO	Change in IPSS, IIEF, and Qmax Identify best candidates for treatment with PDEi based on clinical features	PDEi alone improve IPSS, IIEF, but not Qmax Association of PDEi with ∝-blockers improve IPSS, IIEF, and Qmax
Yan et al[19]	Meta-analysis		515 patients (seven studies)/patients with LUTS/BPO and ED	Compare combination of PDEi with ∝-blockers vs∝-blockers alone. Change IPSS, QoL, BPHII, Qmax, and IIEF	Combination of PDEi with ∝-blockers has additive favorable effects compared with PDEi monotherapy

RCT: Randomized control trial; ED: Erectile dysfunction; LUTS: Lower urinary tract symptoms; IPSS: International prostatic symptoms score; QoL: Quality of life; BPHII: Benign Prostatic Hyperplasia Impact Index; Qmax: Peak flow rate; SEAR: Self-esteem and relationship; EDITS: Erectile Dysfunction Inventory of Treatment Satisfaction Index Score; IIEF: International Index of Erectile Function; PVR: Postvoid residual urine volume; GAQ: Global Assessment Question; BPO: Benign prostatic obstruction; PDEi: Phosphodiesterase inhibitors.