Bayer_Symposium.qxp 25/9/08 11:53 am Page 92
Erectile Dysfunction
Interplay Between Underlying Conditions and determined by the investigator. Efficacy end-points included the
Endothelial Function in Erectile Dysfunction IIEF-EF domain score, per-patient diary response rates to questions on
Patients with ED are unable to achieve and maintain a rigid erection penile insertion (Sexual Encounter Profile [SEP-2]) and maintenance of
because of reduced inflow of blood, excessive outflow or the erection (SEP-3) and rates of positive response to the GAQ.
combination of these conditions. Disruptions of the primary
haemodynamic events that lead to an erection, such as cavernosal For all classifications and for mild to moderate to severe ED, men
arterial inflow (CAI, arterial insufficiency) and corporal veno-occlusive treated with vardenafil 10 or 20mg showed statistically and clinically
dysfunction (CVOD), are major causes of ED. significant improvements in IIEF-EF scores, diary response rates to the
SEP-2 and SEP-3 questions and GAQ compared with the placebo
Hypertension, cardiovascular disease, cerebrovascular accidents, group. The greatest improvements were in patients with more severe
peripheral vascular disease and perineal or penile trauma are all factors ED. The most frequent treatment-emergent adverse events were
that can trigger CAI and CVOD. Hypercholesterolemia also underlies headache, flushing, rhinitis and dyspepsia; these were dose-related,
several vascular aetiologies of ED. Penile arterial inflow through penile mostly mild to moderate in intensity and consistent with the class.
large arteries and smaller arteries (including cavernosal arteries) may be
reduced by atherosclerotic changes secondary to hypercholesterolemia. Vardenafil in Men with Erectile Dysfunction and Diabetes
Endothelial changes associated with hypercholesterolemia may lead to With diabetes being a major underlying co-morbidity for ED,
the disruption of the nitric oxide (NO)/cGMP pathway. Diabetes is Dr Eardley presented data on the impact of vardenafil on diabetes
commonly complicated by vascular problems and ED.
12,13
patients with ED. A prospective, multicentre, double-blind, placebo-
controlled, fixed-dose, parallel-group phase III trial evaluated the
Phosphodiesterase Type-5 Inhibitors – Vardenafil efficacy and safety of vardenafil for ED in men with diabetes.
17
Of
Vardenafil is a potent and highly selective inhibitor of phosphodiesterase the participants, 452 patients with diabetes (type 1 or 2) and ED were
type 5 (PDE5) that increases blood flow to the penis during sexual randomised to take vardenafil 10 or 20mg or placebo for 12 weeks.
stimulation, thus restoring the ability to achieve and sustain erection in Efficacy responses were assessed by IIEF domain scores and a GAQ
men with ED.
14
A number of placebo-controlled studies have about erection improvement during the previous four weeks.
demonstrated the efficacy and safety of vardenafil, irrespective of
patient age or the cause or baseline severity of ED.
15,16
The efficacy and Data analysis 12 weeks post-treatment showed a dose-dependent
safety of vardenafil have also been investigated in men with ED (p=0.02) improvement in erections for the GAQ, with improvement in
and associated underlying conditions. 57 and 72% of men taking 10mg or 20mg vardenafil, respectively,
in contrast to 13% of those in the placebo group (p<0.0001). For the
A retrospective pooled subgroup analysis of randomised, double-blind, erectile function domain, dose-dependent (p=0.03) final scores for the
placebo-controlled studies assessed the safety and efficacy of 10 and 20mg doses were 17.1 and 19.0, respectively, compared with
vardenafil in the treatment of ED in men of different age groups.
15
12.6 for placebo (p<0.0001). Both vardenafil doses significantly
Men from the general population with ED received either placebo or enhanced the rates of successful penetration (p<0.0001) and
vardenafil 5, 10 or 20mg over 12 weeks. Efficacy variables included successful intercourse (p<0.0001) compared with placebo. Vardenafil
the erectile function (EF) domain score from the International Index of treatment was effective in increasing intercourse success rates at all
Erectile Function (IIEF), diary response rates to questions on vaginal levels of baseline ED severity. Treatment-emergent adverse events
penetration and maintenance of erection and positive responses to the were primarily mild to moderate headache, flushing and rhinitis.
Global Assessment Question (GAQ) ‘Has the treatment you have been
taking over the past four weeks improved your erections?’. At 12 The study by Goldstein et al. investigated the efficacy of vardenafil in
weeks the EF domain scores approached 20 with vardenafil and 14 a mixed diabetes population of men with ED. A study by Ziegler et al.
with placebo in men aged ≥65 years (p<0.03 vardenafil 5mg versus focused on type 1 diabetes patients with ED.
18
In this multicentre,
placebo; p<0.001 vardenafil 10 and 20mg versus placebo). The double-blind, placebo-controlled trial, PDE5-inhibitor-naïve patients
corresponding scores were 22 and 14 in men aged 45–64 years and up were randomised to receive placebo or flexible-dose vardenafil
to 24 and 16 in those aged <45 years (p<0.03 vardenafil 5mg versus (5–20mg). The main outcome measures included SEP2 and SEP3,
placebo; p<0.001 vardenafil 10 and 20mg versus placebo). Vardenafil concerning success rates of vaginal insertion and maintenance of
generated positive GAQ responses in approximately 71, 76 and 85% erection to allow successful intercourse, respectively.
of men aged <45, 45–64 and ≥65 years, respectively (p≤0.001
vardenafil versus placebo). The most common treatment-emergent Vardenafil significantly improved mean success rates for SEP2 and SEP3
adverse events were headache, rhinitis, flushing and dyspepsia, which compared with baseline and placebo at four, eight and 12 weeks
were mild to moderate, transient and independent of age. (p<0.0001, intention to treat [ITT] and last observation carried forward
[LOCF]). These rates were unaffected by stratification into distinct subsets
Another retrospective subgroup analysis assessed the effectiveness of according to the level of glycated haemoglobin (HbA
1c
): HbA
1c
<7% =
vardenafil treatment in men with ED of different baseline severity and good glycaemic control, HbA
1c
>7–≤8% = moderate glycaemic control
disease classification.
16
Data from two pivotal, randomised, double- and HbA
1c
>8% = poor glycaemic control. Moreover, vardenafil treatment
blind, placebo-controlled clinical trials enrolling men from the general significantly improved the EF domain score (p<0.0001) of the IIEF
ED population who received placebo or vardenafil 5, 10 or 20mg compared with placebo, demonstrating good responses. These results
during a 12-week period were retrospectively analysed, stratified by demonstrated that vardenafil can significantly improve erectile function in
psychogenic, organic and mixed ED disease classification as type 1 diabetes patients, regardless of the level of glycaemic control.
92 EUROPEAN UROLOGICAL REVIEW
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