PDE-5 Inhibitors Versus Other Treatments

Efficacy. Improvements in erectile function (IIEF-“EF domain” scores) observed in 4 head-to-head trials comparing sildenafil, vardenafil, and tadalafil were inconclusive. In these trials, more patients preferred tadalafil over sildenafil or vardenafil. The mean duration from dosing to attempted sexual intercourse was also longer for tadalafil. The patients' preference in favor of tadalafil could partially be explained by a longer acting duration of tadalafil compared with sildenafil or vardenafil observed in these trials. The half-life for tadalafil, sildenafil, and vardenafil is about 17.5 hours, 4 hours, and 4–5 hours, respectively. Furthermore, unlike sildenafil, the absorption of tadalafil is not influenced by food, making it more convenient.^{390, 391}

Compared with other treatments (i.e., continuous positive air pressure [CPAP], phentolamine, alfuzosin, Ro70–0004), sildenafil was shown to be associated with either statistically significant or numerically greater improvements in the mean IIEF “EF” domain and IIEF-Q3/Q4 scores, the rate of improved erections (GAQ-Q1), and the mean duration of rigidity.(> 60 percent).^{124, 132, 155, 173} The four trials comparing sildenafil to apomorphine^{114, 117, 120, 159} suggest that sildenafil is more effective in improving several outcomes including mean percentage of successful intercourse attempts, mean IIEF scores, and patient satisfaction. Sildenafil had a beneficial clinical effect similar to that of apomorphine in combination with either phentolamine or with phentolamine pluspapaverine.²⁵¹ One explanation for this observed pattern could be that the effect of apomorphine might have been optimized by combining apomorphine with phentolamine alone or also with papaverine.

Harms. The incidence of any adverse events showed no statistically significant difference between patients treated with sildenafil, tadalafil, and vardenafil.^{103, 121, 163} The limited amount of evidence obtained from one trial¹⁰³ suggested that groups treated with sildenafil or tadalafil did not differ in the proportion of patients with serious adverse events. In another trial, ¹²⁴ limited data indicated that fewer patients treated with sildenafil had any adverse events (all-cause) or serious adverse events compared with patients treated with phentolamine. Rates of withdrawal due to adverse events were also numerically lower in the sildenafil groups than in either the phentolamine¹²⁴ or the alfuzosin group.¹⁷³ The incidence of any adverse events in three trials^{114, 117, 120} was poorly reported and was numerically greater in patients treated with sildenafil than in those treated with apomorphine. In one trial, ²⁵¹ the proportion of patients with any adverse events was numerically lower in the sildenafil arm compared with the apomorphine combination arms (with phentolamine).

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