Editorial

10.1517/14656566.6.1.1 © 2005 Ashley Publications Ltd ISSN 1465-6566 1

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Editorial comment on the manuscript entitled ‘Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction’Petros PerimenisUniversity of Patras, Medical School, 26500 Rio, Patras, Greece

Expert Opin. Pharmacother. (2005) 6(1):1–2

The advent of sildenafil and its launch in the market 6 years ago strategicallychanged the diagnostic and therapeutic management of erectile dysfunction (ED)[2,3]. Although very effective and safe in the broad spectrum of patients with ED,sildenafil was followed by two competitors – the newer phosphodiesterase (PDE) 5inhibitors, vardenafil and tadalafil. Therefore, the main issue for physicians andpatients at present is the decision for the best therapeutic choice.

The interesting review of the PDE5 inhibitors by Doggrell [1] summarises theirpharmacodynamic and pharmacokinetic properties and reports on the main resultsof the clinical trials. Given that the three agents have comparable efficacy, theexpert’s opinion focuses on the following conclusions: that sildenafil is consideredthe first treatment choice as more safety and tolerability information is available, aswell as the longer experience with its use; that vardenafil might be substituted forsildenafil in cases where abnormal vision occurred; and that the preference ofpatients for tadalafil over sildenafil might suggest tadalafil as the first choice in thetreatment of ED. This is the current clinical opinion in everyday practice.

Vardenafil appears to be the most potent PDE5 inhibitor biologically, but hassimilar pharmacokinetic properties as sildenafil. In a recent meta-analysis of ran-domised, controlled trials for vardenafil 5, 10 and 20 mg, all efficacy variablesincreased significantly compared with placebo. One of the main conclusions of thissystematic review is that more data are needed on subgroups of patients [4]. Vardena-fil is safe, although abnormal vision, occurring in < 1% of patients, is associated withthe drug [5]. However, practically, the drug-related colour vision disturbances do notseem to be an important issue. I have not encountered a man successfully treatedwith a PDE5 inhibitor who would switch to another drug because of abnormalvision. The lack of head-to-head comparative studies between PDE5 inhibitorsrestricts the ability of physicians to identify whether the biological potency of varde-nafil results in higher clinical efficacy. Therefore, why prescribe vardenafil instead ofsildenafil, which has been used successfully by many millions of men in > 110 coun-tries, and has been co-administered safely with several medications by men with anumber of comorbidities?

Tadalafil is pharmacologically distinguished from the other PDE5 inhibitors by itslonger half-life of 17.5 versus ∼ 4 h, and its independence of food consumption. Thisproperty seems to correspond with prolonged clinical efficacy. Porst et al. [6] reportedon the significant ability for successful intercourse up to 36 h after dosing. In somecases, such as in those at risk for cardiovascular events, the prolonged efficacy must bebalanced against possible side effects due to the long-lasting drug concentrations.However, the long half-life of tadalafil offers a wider window for successful sexualperformance and couples take this advantage [7]. This is possibly the most important

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Editorial comment on the manuscript entitled ‘Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction’

2 Expert Opin. Pharmacother. (2005) 6(1)

issue, because without the pressure of time, the sexualself-confidence of the man may strengthen and the couple mayact spontaneously. The preference studies between tadalafiland sildenafil, although with design defects, showed that menpreferred tadalafil. This fact was evidently due to the dosinginstructions and the consequent advantages of tadalafil. How-ever, in a recent study of the extension of the effectiveness ofsildenafil in a population of treatment responders, 75% of thepatients were found to respond 12 h after dosing [8]. Althoughthis finding is observed in andrologists’ clinical practice, thistrial challenges clinicians to re-explore the therapeutic windowof PDE5 inhibitors with a short half-life, in order to documenteffectiveness beyond the commonly believed view, and

suggested a 4-h period. If this occurs, what will actually be theadvantage of tadalafil over sildenafil?

As indicated in the review by Doggrell [1], the data, ∼ 2 yearsafter the launch of the newer PDE5 inhibitors, show that allagents have more or less the same efficacy and basically thesame drug class-related safety profile. Because of the lack ofappropriate studies, the evident difference supporting one’sopinion for a superior therapeutic choice is minor, if any. In myopinion, as long as the therapeutic tools exist, the professionalprofile of the physician may elevate drug efficacy. A dedicatedand instructive physician, who can set realistic expectations andencourage couples to comply with treatment, will make thetrue difference.

BibliographyPapers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

1. DOGGRELL SA: Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. Expert Opin. Pharmacother. (2005) 6(1):75-84.

2. PERIMENIS P, ATHANASOPOULOS A, GYFTOPOULOS K, BARBALIAS G: Sildenafil test: changes in the diagnostic and therapeutic management of erectile dysfunction. Int. Urol. Nephrol. (2001) 33:387-389.

3. PADMA-NATHAN H, STEERS WD, WICKER PA, for the Sildenafil Study Group: Efficacy and safety of oral sildenafil in the treatment of erectile dysfunction: a double-blind, placebo-controlled study of 329 patients. Int. J. Clin. Pract. (1998) 52:375-379.

4. MARKOU S, PERIMENIS P, GYFTOPOULOS K, ATHANASOPOULOS A, BARBALIAS G: Vardenafil (Levitra) for erectile dysfunction: a systematic review and meta-analysis of clinical trial reports. Int. J. Impot. Res. (2004) 16(6):470-478.

• A systematic review and meta-analysis of randomised, controlled trials on vardenafil.

5. HELLSTROM WJG: Vardenafil: a new approach to the treatment of erectile dysfunction. Cur. Urol. Reports (2003) 4:479-487.

6. PORST H, PADMA-NATHAN H, GIULIANO F, ANGLIN G, VARANESE L, ROSEN R: Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology (2003) 62:121-126.

• A multi-centre assessment of the efficacy of tadalafil at several time periods after dosing.

7. CARSON CC, RAJFER J, EARDLEY I et al.: The efficacy and safety of tadalafil: an update. BJU International (2004) 93:1276-1281.

• An interesting update on the efficacy and safety of tadalafil in the treatment of 2102 men, included in 11 randomised, controlled clinical trials.

8. MONCADA I, JARA J, SUBIRA D, CASTANO I, HERNANDEZ C: Efficacy of sildenafil citrate at 12 hours after dosing: re-exploring the therapeutic window. Eur. Urol. (2004) 46:357-361.

AffiliationPetros PerimenisUniversity of Patras, Medical School, 26500 Rio, Patras, GreeceTel: +30 2610 994 668; Fax: +30 2610 994 668;E-mail: petperim@upatras.gr