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

Table 3 Studies evaluating the combination of phosphodiesterase inhibitors and alpha-blockers in patients with lower urinary tract symptoms

Ref.	Design of study	Placebo run-in	Participant /Inclusion criteria	End point	Major conclusion
Oelke et al[44]	Randomized, multicentric, placebo controlled, and parallel-group	Yes	Men ≥ 45 yr of age with BPO/LUTS, IPSS ≥ 13, and Qmax between 4-15 mL/s 512 men were randomized to placebo (n = 172), tadalafil 5 mg (n = 171) or tamsulosin 0.4 mg (n = 168); Men ≥ 45 yr of age with BPO/LUTS, IPSS ≥ 13, and Qmax between 4-15 mL/s	Compare effect of tadalafil 5 mg once daily with placebo on BPO/LUTS	Tadalafil 5 mg and tamsulosin 0.4 mg had similar improvement in BPO/LUTS and Qmax compared with placebo However, only tadalafil caused a significant improvement in QoL, treatment satisfaction, and erectile function
Regadas et al[45]	Randomized, double-blind, and placebo controlled	No	Men ≥ 45 yr of age, BOOI ≥ 20 and IPSS ≥ 14 A total of 40 men were randomized to tadalafil 5 mg/tamsulosin 0.4 mg (n = 20) or tamsulosin 0.4 mg /placebo (n = 20) Men ≥ 45 yr of age, BOOI ≥ 20 and IPSS ≥ 14	Observe changes in urodynamic variables (Qmax and PdetQmax)	Combination of tamsulosin/tadalafil decrease after-load (pdetQmax) and has potential to protect detrusor smooth muscle Additionally, the combination resulted in a significant improvement in IPSS compared with tamsulosin/placebo
Bechara et al[46]	Randomized, double-blind, and crossover study	No	History of LUTS/BPO of at least six months Thirty men were randomized to tamsulosin 0.4 mg or tamsulosin 0.4 mg/tadalafil 20 mg daily History of LUTS/BPO of at least six months	Acess efficacy and safety of combination of tamsulosin with tadalafil compared with tamsulosin alone	Combination therapy had more significative impact in IPSS and ED compared with tamsulosin alone
Kaplan et al[39]	Randomized, double-blind study	No	Men aged 50-76 yr with untreated LUTS and ED Sixty two patients were randomized to receive alfuzosin 10 mg (n = 20), sildenafil 25 mg (n = 21), or a combination of both (n = 20) Men aged 50-76 yr with untreated LUTS and ED	Acess efficacy and safety of combination of alfuzosin with sildenafil	Only sildenafil or combination improve ED Improvement in IPSS was observed with three treatments
Gacci et al[47]	Randomized, double-blind placebo-controlled trial	Yes	Men with persistent storage LUTS Sixty men were randomized to tamsulosin 0.4 mg or tamsulosin 0.4 mg/vardenafil 10 mg Men with persistent storage LUTS	Acess efficacy and safety of combination of tamsulosin with vardenafil	Combination therapy had more significative impact in IPSS and ED compared with tamsulosin alone

BPO/LUTS: Benign prostatic hyperplasia/lower urinary tract symptoms; Qmax: Peak flow rate; QoL: Quality of life; IPSS: International Prostatic Symptoms Score; PdetQmax: Detrusor pressure at maximum flow; ED: Erectile dysfunction; BOOI: Bladder outlet obstruction index.