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Hatzimouratidis K, Moysidis K, Bekos A, Tsimtsiou Z, Ioannidis E, Hatzichristou D. Treatment strategy for "non-responders" to tadalafil and vardenafil: a real-life study. Eur Urol 2006;50:126-132.

This is a topical study of everyday clinical relevance which advocates a treatment strategy for non-responders to the 2 newer PDE5 Inhibitors, Vardenafil and Tadalafil

Method
Two groups [tadalafil-treated (TG); vardenafil-treated (VG)] of 100 consecutive patients complaining of non-response to treatments were enrolled in three-phase study. Phase 1: inadequate use was identified and patients were rechallenged, after receiving detailed usage information. Phase 2: true non-responders were given new instructions based on drugs’ pharmacologic profiles: TGs were dosed at least 2 h before intercourse; VGs were dosed only in fasted state. Remaining non-responders entered phase 3: continuous administration of 20 mg tadalafil every other day, or 20 mg vardenafil every day for 2 weeks. Efficacy was based on positive (yes) response to two questions: ‘‘Were your erections rigid, and did they last long enough to have successful intercourse?’’ and ‘‘Do you want to repeat your prescription?’’

Results
Tadalafil group: Inappropriate use was recognized in 32 patients; 14
(43.75%) responded after adequate instruction. Phase 2: 32 of 86 (37.2%) had intercourse at least 2 h after dose intake. Phase 3: 6 of 86 (11.1%) responded to continuous administration. Overall salvage rate was52 of 100 (52%).

Vardenafil group: Inappropriate use was recognized in 38 patients; 12 (31.58%) responded after adequate instruction. Phase 2, 22 of 88 (25%) responded to dosing in a fasted state. Phase 3: 12 of 66 (18.2%) responded to daily dosing. Overall salvage rate was 46 of 100 (46%).

In conclusion, following proposed treatment strategy may maximize response rate to phosphodiesterase 5 inhibitors; appropriate usage instructions may play significant role in response rate.

The authors present a well designed 3 phase study which evaluates the efficacy of Tadalafil and Vardenafil in a group of patients with previous treatment failure by using the above mentioned drugs with a newly proposed management strategy. Results on appropriate information regarding medications and adequate dosing, 12% of non-responders in vardenafil group and 14% - in tadalafil group were converted to responders.

The outcome of Phase II is of a particular interest as 37.2% of patients became treatment responders with administration of tadalafil at least 2 h before the intercourse; and in the other group of patients 25% converted to responders while taking vardenafil in a fasted state. Such administration scheme for new PDE5i is probably applied by some professionals in everyday practice; however, this study first has described and obviously confirmed the evident, which should be considered in ED patient management. With the treatment administration for 2 consecutive weeks, a positive response was reported among 15% of previously failed men. It is disputable, whether the effect of continuous administration was influencing the phase II outcomes of the study as well as continuation of phase I in to phase II was done without washout period; although, as it mentioned by the authors, designed as a real life study, they were avoiding limitations.