Efficacy of PDE-5-inhibitors for erectile dysfunction. A comparative meta-analysis of fixed-dose regimen randomized controlled trials administering the International Index of Erectile Function in broad-spectrum populations

Article (PDF Available)inInternational Journal of Impotence Research 18(3):229-35 · October 2005with142 Reads
DOI: 10.1038/sj.ijir.3901395 · Source: PubMed
Abstract
This meta-analytic study aims to estimate the likely improvements of erectile dysfunction (ED) measured by the International Index of Erectile Function (IIEF) at the highest fixed dosages of the three available PDE-5-inhibitors: sildenafil, tadalafil, and vardenafil. MEDLINE and the Cochrane Library were searched electronically for efficacy trials of PDE-5-inhibitors for treating ED. In addition drug manufacturers were contacted to provide unpublished or unrecorded congress proceedings. Randomized, double-blind, placebo-controlled, parallel-group, maximum fixed-dose, broad-spectrum efficacy trials using IIEF were included in the analysis. Data were independently extracted by two reviewers. The results were pooled using weighted mean differences. A formal indirect comparison (including Bonferroni-correction) was conducted to estimate the differences between agents. A total of 14 trials were included in the meta-analysis (three with 100 mg sildenafil, eight with 20-25 mg tadalafil, and three with 20 mg vardenafil). All trials were of good methodological quality. Overall heterogeneity was moderate: I(2)=33.2%, chi(2)=19.47, P=0.11. The funnel plot suggested moderate likelihood of publication bias. Pooled results of IIEF-improvement were for sildenafil 9.65 (95% CI: 8.50, 10.79) points, tadalafil 8.52 (7.61, 9.42) points, and vardenafil 7.50 (6.50, 8.50) points, respectively. Sildenafil proved to be significantly more effective than vardenafil (d=2.15, P=0.006), other pairwise comparisons showed no difference in efficacy. All PDE-5-inhibitors are highly effective in the treatment of ED. At maximum dosage they improve erectile function 7-10 points on the IIEF compared to placebo-treatment. There is evidence that sildenafil might be more efficacious than vardenafil, although this is to be interpreted with caution. To prove higher efficacy truly independent comparative trials are needed.
REVIEW
Efficacy of PDE-5-inhibitors for erectile dysfunction.
A comparative meta-analysis of fixed-dose regimen randomized
controlled trials administering the International Index of Erectile
Function in broad-spectrum populations
MM Berner, L Kriston and A Harms
Department of Psychiatry and Psychotherapy, University Medical Center, Freiburg, Germany
This meta-analytic study aims to estimate the likely improvements of erectile dysfunction (ED)
measured by the International Index of Erectile Function (IIEF) at the highest fixed dosages of the
three available PDE-5-inhibitors: sildenafil, tadalafil, and vardenafil. MEDLINE and the Cochrane
Library were searched electronically for efficacy trials of PDE-5-inhibitors for treating ED. In
addition drug manufacturers were contacted to provide unpublished or unrecorded congress
proceedings. Randomized, double-blind, placebo-controlled, parallel-group, maximum fixed-dose,
broad-spectrum efficacy trials using IIEF were included in the analysis. Data were independently
extracted by two reviewers. The results were pooled using weighted mean differences. A formal
indirect comparison (including Bonferroni-correction) was conducted to estimate the differences
between agents. A total of 14 trials were included in the meta-analysis (three with 100 mg sildenafil,
eight with 20–25 mg tadalafil, and three with 20 mg vardenafil). All trials were of good
methodological quality. Overall heterogeneity was moderate: I
2
¼ 33.2%, v
2
¼ 19.47, P ¼ 0.11. The
funnel plot suggested moderate likelihood of publication bias. Pooled results of IIEF-improvement
were for sildenafil 9.65 (95% CI: 8.50, 10.79) points, tadalafil 8.52 (7.61, 9.42) points, and vardenafil
7.50 (6.50, 8.50) points, respectively. Sildenafil proved to be significantly more effective than
vardenafil (d ¼ 2.15, P ¼ 0.006), other pairwise comparisons showed no difference in efficacy. All
PDE-5-inhibitors are highly effective in the treatment of ED. At maximum dosage they improve
erectile function 7–10 points on the IIEF compared to placebo-treatment. There is evidence that
sildenafil might be more efficacious than vardenafil, although this is to be interpreted with caution.
To prove higher efficacy truly independent comparative trials are needed.
International Journal of Impotence Research (2006) 18, 229–235. doi:10.1038/sj.ijir.3901395;
published online 20 October 2005
Keywords: impotence; phosphodiesterase inhibitors; meta-analysis; treatment outcome; rando-
mized controlled trials
Introduction
According to high-quality international community-
based epidemiological studies, erectile dysfunction
(ED), the difficulty in developing or maintaining an
erection suitable for satisfactory intercourse, affects
around 16% of the men all over the world.
1,2
However,
some estimates range up to 27%.
3,4
When using ad
hoc definitions of ED reported prevalence rates exceed
40% (for summary see Kubin et al.
5
). The prevalence
of ED increases with age as well as with comorbid
conditions including cardiovascular diseases, dia-
betes, neurological diseases, and depression.
1,2,5
There are several treatments for ED, such as
hormone compounds, ointments, vacuum-constric-
tion devices, intracavernosal injections of vasoactive
agents, transurethral delivery of alprostadil, implan-
tation of penile prostheses, venous or arterial
surgery, and psychotherapeutic methods. Neverthe-
less, with the approval of sildenafil, a phosphodies-
terase-5 (PDE-5) inhibitor, in 1998 an oral therapy
for ED became available in the US that soon found
worldwide acceptance. With the appearance of two
other PDE-5 inhibitors, tadalafil and vardenafil in
Received 25 July 2005; revised 13 August 2005; accepted
14 August 2005; published online 20 October 2005
Correspondence: Dr MM Berner, Department of Psychiatry
and Psychotherapy, University Medical Center, Haupt-
strasse 5, Freiburg 79115, Germany.
E-mail: Michael_Berner@psyallg.ukl.uni-freiburg.de
International Journal of Impotence Research (2006) 18, 229235
&
2006 Nature Publishing Group All rights reserved 0955-9930/06 $30.00
www.nature.com/ijir
2003, a competitive situation emerged, which was
described by Wyllie as ‘the phosphodiesterase
inhibitor war’.
6
In his opinion, in 2003 it was high
time to see, what the new agents (tadalafil and
vardenafil) could and would add to treatment of
ED.
6
One aspect of this question, the topic of
efficacy is the focus of the present meta-analysis.
Using evidence-based medicine (EBM) terms to
date efficacy of sildenafil is empirically supported
on the level I.A., that is, based on systematic
review(s).
7–9
The efficacy of tadalafil
10
and varde-
nafil
11–15
is supported by evidence level I.B., that is,
based on high-quality randomized controlled trials
(RCT). In these studies all three agents display both
statistically as well as clinically significant improve-
ment in erectile functioning.
In efficacy trials of treatments for ED numerous
outcome measures exist. Besides physiological
assessments, such as penile rigidity (RigiScan
16
),
physician- (e.g. clinician’s global impression (CGI))
and patient-rated instruments are available. General
efficacy assessment questions (often abbreviated as
GAQ, GEQ or GEAQ), for example, ‘Has the treat-
ment improved your erections?’, are often preferred
and presented as primary outcome to researchers,
physicians and patients. Patient diaries (event logs),
such as the sexual encounter profile (SEP), are also
frequently used to assess ‘proportion of successful
intercourse attempts’ or ‘proportion of patients with
at least one successful intercourse attempt’ as
outcomes. Patient questionnaires (e.g. International
Index of Erectile Function (IIEF)
17
) are available and
can be analyzed either as items or as scales. The
latter is used in almost all newer studies of PDE-5-
inhibitors. Most studies use more than one outcome
for efficacy assessment.
The objective of the present meta-analysis is to
evaluate the efficacy of the available PDE-5 inhibi-
tors for ED and to assess possible difference between
these agents using the Erectile Function Domain
Score of the IIEF.
17
Materials and methods
Literature search
In July 2004, the MEDLINE and the Cochrane
Central Register of Controlled Trials (CENTRAL)
databases were searched for efficacy trials of
sildenafil, tadalafil, and vardenafil. In the electronic
search the substance and trade names were com-
bined with the truncated terms ‘effic*’ and ‘effec*’.
This highly sensitive strategy should enable a more
extensive retrieval of relevant studies, than more
restricted searches (e.g. by spectrum of disease or
outcomes). Additionally, the website of the US Food
and Drug Administration/Center for Drug Evalua-
tion and Research was searched for approval studies
since in many cases some approval studies are not
available in a published format.
The national branches of drug manufacturers of
the three examined agents were contacted to provide
additional information, such as unpublished con-
gress proceedings. Reference lists of all relevant
publications were searched for possible additional
papers (ancestry approach).
Inclusion of trials
Titles and abstracts of all identified publications
were screened independently by two reviewers (LK
and AH). Trials were included, when they fulfilled
all of the following criteria: (1) randomized and
controlled by placebo (RCT); (2) parallel-group
design; (3) double-blinding; (4) administering the
maximum fixed-dose regimen of the agent (sildena-
fil 100 mg, tadalafil 20–25 mg, vardenafil 20 mg);
(5) conduction in broad-spectrum sample with ED;
(6) administering the IIEF;
17
(7) reporting relevant
outcome, at least mean and sample size. When
decision about inclusion was impossible on the
basis of the abstract, the full text was acquired. Any
disagreement between reviewers was resolved by
involving a third reviewer (MB) to decide.
Data extraction and assessment of methodological
quality
Basic data were extracted by LK using a structured
form that included the following information:
authors; year of publication; language; country;
agent; daily dose; duration of treatment; sample
size; age; ethnicity; duration of ED; cause of ED; and
baseline severity of ED in patient population.
Methodological quality was assessed by LK by
means of the Jadad Score.
18
Due to the inclusion
criteria (randomization and double-blinding) all
studies scored at least two points on Jadad’s scale.
Further three points could be obtained by describing
the (appropriate) randomization, (appropriate) dou-
ble-blinding method and the study withdrawals. If
study report was brief (e.g. only abstract available),
methodological quality was not assessed.
Outcome reports were extracted independently by
two reviewers (LK and AH). Any disagreement was
resolved by discussion.
In case of insufficiently reported data, standard
deviations were substituted. The estimation was
based either on figures presenting confidence inter-
vals, standard errors or standard deviations or on
other studies with the same agent, which reported
s.d. for treatment and placebo group. Means and
sample sizes were not substituted, insufficient
reporting led to study exclusion.
Statistical analysis
The outcome of the present meta-analysis was the
Erectile Function (EF) domain score of IIEF.
17
We
Efficacy of PDE-5-inhibitors for erectile dysfunction
MM Berner et al
230
International Journal of Impotence Research
chose this parameter because of several reasons.
First, it is collected from the patient, providing
direct data from the affected person. Second, it is
a psychometrically tested instrument that validly
and reliably measures several aspects of erectile
functioning. Third, its continuous character allows
a differentiated assessment of the ED (in contrast
to categorizing patients in ‘responder’ and ‘non-
responder’), as well as the application of more
sophisticated statistical methods. And fourth, it is
a widespread assessment of disease severity in
efficacy trials concerning ED. The EF domain score
can range from 1 to 30.
For meta-analysis, weighted mean differences
(WMD) between agent and placebo group in the EF
domain score after treatment were calculated. As the
stringent inclusion criteria probably led to reduced
clinical heterogeneity, we also assumed a low
statistical heterogeneity in primary study findings.
We, therefore, used a fixed-effect model for pooling
the data. Statistical heterogeneity was assessed by
w
2
-andI
2
-statistics. I
2
indicates the percentage of the
heterogeneity in effect estimates that is due to clinical
or methodological diversity rather than chance.
19
At the time of performing the present meta-
analysis there was no information available from
independent high-quality direct-comparative trials.
Efficacy of sildenafil, tadalafil, and vardenafil was
therefore indirectly compared using formal (statis-
tical) methods suggested by several experts.
20–22
The chosen procedure bases on the assumption,
that agents are comparable through their relative
effect vs a common comparator. In the present case
it is placebo. In the analysis Bonferroni-correction
of level of significance for multiple testing was
carried out.
To test for possible publication bias, visual exam-
ination of funnel plot (scatter plot of effect size and
the reciprocal standard error) was performed.
During the review process it was noted, that the
highest fixed-dose regimen in case of tadalafil
was not sufficiently defined. In some trials 25 mg
tadalafil were administered, although the highest
approved regimen in the US is 20 mg. Therefore, a
post hoc decision was made to perform a sensitivity
analysis with and without these trials.
Data analysis was performed with Review Man-
ager 4.2, the Statistical Package for Social Sciences
(SPSS) 11.5 and Microsoft Excel 8.0.
Results
Identification of trials
Literature search retrieved 75 double-blind parallel
group RCTs that evaluated efficacy of sildenafil,
tadalafil, or vardenafil (see Figure 1). For sildenafil,
five relevant studies were identified. Three of them
were included in the meta-analysis
23–25
and two
were excluded due to insufficiently reported
data.
26,27
A significant number of sildenafil studies
were conducted before the development of the IIEF
and were consequently excluded. Several studies
could not be included due to the usage of flexible-
dose regimen.
For tadalafil, eight studies were included in the
analysis. Three of them were published in medical
journals
28–30
and five were abstracted from the
documentation of the US National Food and Drug
Administration.
31
Three of these approval studies
were already directly pooled in an analysis and
published also elsewhere.
10
For vardenafil, three trials were included in the
meta-analysis. Two of them were published in
medical journals.
11,12
One of them is an approval
study that was also published a second time
elsewhere.
11,32,33
The third study was extracted
from the documentation of the US National Food
and Drug Administration.
33
Altogether 14 studies with a total of 4836 patients
were included in the meta-analysis (Figure 1).
Characteristics and methodological quality of the
included trials is presented in Table 1.
Data synthesis
The main results of the meta-analysis are shown in
Figure 2. Pooled findings for sildenafil resulted in
double blind parallel group efficacy RCTs (n=75)
sildenafil 51 tadalafil 17 vardenafil 7
IIEF as outcome (n=47)
sildenafil 28 tadalafil 12 vardenafil 7
broad spectrum sample (n=28)
sildenafil 13 tadalafil 10 vardenafil 5
fixed-dose regimen (n=19)
sildenafil 5 tadalafil 10 vardenafil 4
highest fixed-dose regimen (n=16)
sildenafil 5 tadalafil 8 vardenafil 3
included in meta-analysis (n=14)
sildenafil 3 tadalafil 8 vardenafil 3
IIEF not used in assessment (n=28)
selected samples (n=19)
flexible-dose regimen (n=9)
highest fixed-dose not used (n=3)
data not extractable (n=2)
Figure 1 Identification of studies.
Efficacy of PDE-5-inhibitors for erectile dysfunction
MM Berner et al
231
International Journal of Impotence Research
an effect of 9.65 (8.50, 10.79) points improvement.
Heterogeneity between trial results was minimal
(w
2
¼ 0.03, P ¼ 0.99, I
2
¼ 0%).
Findings of eight tadalafil studies could be pooled
into an effect of 8.52 (7.61, 9.42) points improve-
ment. Minor but not substantial heterogeneity was
present in the data (w
2
¼ 10.63, P ¼ 0.16, I
2
¼ 34.1%).
Vardenafil showed an effect of 7.50 (6.50, 8.50)
points improvement in a homogenous study sample
(w
2
¼ 1.17, P ¼ 0.56, I
2
¼ 0%).
Combining all studies lead to an estimated effect
size of 8.46 (7.88, 9.04) points improvement. The
whole data set was slightly heterogeneous
(w
2
¼ 19.47, P ¼ 0.11, I
2
¼ 33.2%).
In pairwise comparisons no significant difference
was found between sildenafil and tadalafil
(difference(d) ¼ 1.13 points, P ¼ 0.132)aswellas
between tadalafil and vardenafil (d ¼ 1.02 points,
P ¼ 0.140). Sildenafil proved to be significantly more
efficacious than vardenafil (d ¼ 2.15 points, P ¼ 0.006).
Visual examination of the funnel plot (Figure 3)
suggested moderate likelihood of publication
bias both for individual agents and for all studies,
although results rest on a limited number of studies.
Sensitivity analysis with the exclusion of studies, in
which a tadalafil dose of 25 mg was administered lead
to a minor reduction of heterogeneity in the tadalafil
study sample (I
2
¼ 29.2%). Although there was some
tendency favoring sildenafil over tadalafil it did not
prove a significant effect on pairwise comparisons
(sildenafil vs tadalafil: d ¼ 1.50, P ¼ 0.054; tadalafil vs
vardenafil: d ¼ 0.65, P ¼ 0.367).
Discussion
The present meta-analysis assesses the efficacy
of the three available PDE-5 inhibitors (sildenafil,
tadalafil, and vardenafil) for the treatment of ED. Its
main limitation results from the fact, that it is not an
overall systematic review, but merely a comparative
meta-analysis of the best available evidence using
the highest possible meta-analytic methodological
standards. Thus it cannot provide an overall
evaluation of all therapeutic properties of the three
oral agents for ED. We aimed merely at one single
efficacy outcome, the erectile function domain score
of the IIEF.
17
Although it is valid and reliable, in
terms of ‘objective’ clinical epidemiology the best
available outcome measure. But it cannot be ex-
cluded that other especially generically created
outcome measures might have led to different
results. In addition, we chose not to evaluate
adverse effects and discontinuation rates, although
these undesirable outcomes are important for the
individual patient decision to favor one treatment
over another. Other relevant aspects, such as onset
latency, half-life or patient preference, were also not
considered.
Nevertheless, some essential statements can be
made based on this meta-analysis. First, there is no
doubt, that all PDE-5 inhibitors are highly effica-
cious. An 8.5 point improvement in comparison to
the control group is large enough, to successfully
treat severe ED. Second, there seem to be possible
efficacy differences between agents, mainly the
statistically significant superiority of sildenafil over
vardenafil. Although it might be too speculative to
consider them as clinically relevant for an indivi-
dual patient choice they might become more
important in larger perspectives, for example, in
cost-benefit analyses.
Since the comparison was carried out indirectly
an important question with respect to the internal
validity of the present meta-analysis is the compar-
ability of the studies that evaluate the different
Table 1 Characteristics of included studies
First author, year of publication Ref. Drug, dose
(mg)
Treatment
duration
(weeks)
Study population Mean
age
(years)
ED etiology
organic/
psychogenic
EF
baseline
score
Jadad-
score
Montorsi, 1999
23
Sildenafil, 100 12 514 men 56 32%/25% 12.6 3
Shirai, 2000
25
Sildenafil, 100 8 256 Japanese men 53 18%/29% 10.0 NE
Padma-Nathan, 2003
24
Sildenafil, 100 4 228 men 63 64%/3% 13.3 3
Padma-Nathan, 2001
30
Tadalafil, 25 3 179 men 56 NE 15.0 3
Faria, 2003
29
Tadalafil, 20 12 204 Brazilian men 54 31%/22% 16.1 NE
(Approval study LVCO), 2004
31
Tadalafil, 20 12 197 Taiwanese men 60 NE 15.6 3
(Approval study LVCQ), 2004
31
Tadalafil, 20 12 140 Australian men 59 42%/8% 15.6 3
(Approval study LVDJ), 2004
31
Tadalafil, 20 12 253 Canadian men 59 59%/NE 15.0 3
(Approval study USA A), 2004
a31
Tadalafil, 20 12 402 American men 59 NE 13.1 NE
(Approval study USA B), 2004
a31
Brock, 2001
28
Tadalafil, 25 8 212 men 58 NE 15.1 NE
Porst, 2001
12
Vardenafil, 20 12 601 men 52 32%/26% 14.0 3
Hellstrom, 2002
11
Vardenafil, 20 26 805 men 57 57%/7% 12.9 4
[Approval study 10128], 2003
33
Vardenafil, 20 12 845 men 55 NE 13.1 3
Ref.: reference; NE: not eligible.
a
Characteristics available only pooled for both studies.
Efficacy of PDE-5-inhibitors for erectile dysfunction
MM Berner et al
232
International Journal of Impotence Research
agents. The differences that were found might be
caused by other factors than the agent itself, such
as baseline ED severity, etiology, age, ethnicity, or
treatment history.
34
To finally evaluate the likely
differences between agents truly independent com-
parative trials are necessary.
This possible shortcoming with respect to internal
validity, however, has some advantage considering
external validity, that is, generalizibility of the
results. The use of unselected, community-based
patient samples with various etiologies, age, co-
morbid conditions, ethnicity etc. allows to establish
an efficacy prove for a broad spectrum of patients
suffering from ED. This finding is also supported
by a very low heterogeneity in the primary study
results. With this respect, the present findings
might support evidence not only for efficacy,
but to a certain degree also for effectiveness in every-
day practice, although highest dosage of these drugs
may not be always be used. Effectiveness of the
agents is also confirmed in open-label naturalistic
studies.
35–37
After establishing evidence for efficacy and
pointing out towards possible efficacy differences,
further information is needed in questions that
mainly affect patient’s compliance and preferences.
This might include the effects on quality of life (e.g.
effects on relationship issues), likely predictors of
(non)compliance (e.g. myths about dangerous side
effects) and true patient preferences (e.g. realistic
desired frequency of intercourse). Indeed, the most
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0123456789101112
WMD
1/SE
tadalafil
sildenafil
vardenafil
pooled effect size
Figure 3 Funnel plot. SE: standard error; WMD: weighted mean
difference.
ALL SILDENAFIL
Padma-Nathan, 2003
Shirai, 2000
Montorsi, 1999
9.65 (8.50, 10.79)
9.36 (5.83, 12.89)
9.68 (7.76, 11.60)
9.68 (8.11, 11.25)
ALL TADALAFIL
Brock, 2001
Appr. study USA B,2004
Appr. study USA A,2004
Appr. study LVDJ, 2004
Appr. study LVCQ, 2004
Appr. study LVCO, 2004
Faria, 2003
Padma-Nathan, 2001
8.52 (7.61, 9.42)
11.00 (8.04, 13.96)
8.90 (6.54, 11.26)
6.00 (3.63, 8.37)
8.80 (6.32, 11.28)
10.10 (7.54, 12.66)
6.90 (4.41, 9.39)
8.40 (6.00, 10.80)
9.50 (6.17, 12.83)
ALL VARDENAFIL
Appr. study 10128, 2003
Hellstrom, 2002
Porst, 2001
7.50 (6.50, 8.50)
8.26 (6.54, 9.98)
7.00 (5.19, 8.81)
7.20 (5.51, 8.89)
ALL STUDIES
8.46 (7.88, 9.04)
WMD (95% CI)
-5 0 10 155
Wei
g
hted Mean Difference (95% CI)
Study, year
Figure 2 Forrest plot for efficacy of PDE-5-inhibitors.
Efficacy of PDE-5-inhibitors for erectile dysfunction
MM Berner et al
233
International Journal of Impotence Research
essential step to overcome ‘the phosphodiesterase
inhibitor war’
6
would be to establish a shared-
decision health care model that is oriented towards
the patient’s needs rather than marketing interests
of third parties and a medicalization of the couple’s
sexuality.
Conflict of interest
There was no specific funding for this project. MB
currently holds research grants from the German
Ministry for Education and Research, Boehringer
Ingelheim Inc., Pfizer Inc. and Willmar Schwabe
Inc. He did receive tuition fees from Glaxo Smith
Kline, Hormosan Kwizda, Lilly, Pfizer and Willmar
Schwabe. He also received travel expenses from the
European Sexual Dysfunction Alliance affiliate (ISG
e.V.) that receives sponsoring from the pharmaceu-
tical industry. LK did receive travel expenses reim-
bursement from Pfizer and Wilmar Schwabe. AH
holds a paid part time position with the European
Sexual Dysfunction Alliance affiliate (ISG e.V.).
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    • "Though a subjective preference for tadalafil has already been demonstrated in a handful of studies, at the same time several lines of evidence implementing evaluation of PDE-5Is action with the International Index of Erectile Function (IIEF) have shown no predilection at all. In a meta-analysis comparing 14 trials with PDE-5Is, pooled results between sildenafil, vardenafil and tadalafil were almost comparable [71]. In another open-label, randomized, multicenter, crossover study conducted by Jannini et al, an overall equivalence in the subjective perception of treatment benefits for all PDE-5Is tested was demonstrated [72]. "
    [Show abstract] [Hide abstract] ABSTRACT: Erectile dysfunction is usually of vascular origin and is frequently encountered in men with cardiovascular disease. The introduction of phosphodiesterase-5 inhibitors has revolutionized the management of patients with erectile dysfunction. Currently available phosphodiesterase-5 inhibitors have distinct pharmacokinetic and pharmacodynamic properties, thus permitting for tailoring sexual therapy according to patient characteristics and needs. Phosphodiesterase-5 inhibitors possess vasorelaxing properties and exert systemic hemodynamic effects, which need to be taken into account when other cardiovascular drugs are co-administered. Special caution is needed with alpha-blockers, while the co-administration with nitrates is contra-indicated due to the risk of life-threatening hypotension. This review presents the advent of sexual therapy, describes the mechanism of action and the specific characteristics of commercially available phosphodiesterase-5 inhibitors, summarizes the efficacy and safety of these drugs with special emphasis on the cardiovascular system, and discusses the clinical criteria used for the selection of each drug for the individual patient.
    Full-text · Article · Nov 2014
    • "Preclinical studies demonstrated that the selectivity of mirodenafil toward PDE5 was 10-fold higher than that of sildenafil, whereas its inhibitory effects on other PDEs were much lower than those of sildenafil [10,20]. A previous meta-analysis have demonstrated that compared to placebo, sildenafil generated an obvious improvement about 9.65 points, tadalafil could be pooled into an effect of 8.52 points improvement, vardenafil leaded to an effect of 7.50 points improvement in IIEF EFD score and udenafil resulted in an effect of 8.62-point improvement [21,22]. In this study, 100 mg mirodenafil resulted in an effect of 7.32 points improvement. "
    [Show abstract] [Hide abstract] ABSTRACT: Aim: To systematically review evidence on the efficacy and safety of mirodenafil treatment in erectile dysfunction (ED) from randomised controlled trials. Methods: We searched PubMed, Embase and the Cochrane Library database up to March 2013. Two authors independently assessed study quality and extracted data. All data were analyzed using RevMan 5.0. Outcome measures assessed were the International Index of Erectile Function (IIEF), erectile function domain (EFD) score (primary), the Sexual Encounter Profile questions 2 and 3, and the response to the Global Assessment Questionnaire and adverse effects (secondary). Results: A total of 374 participants from three randomized controlled trials were identified in this meta-analysis. After 12 weeks treatment, mirodenafil was found to be more effective than placebo, and tolerability was good. The pooled results showed that the IIEF EFD score for 100 mg mirodenafil group was higher than placebo group (MD = 8.13, 95%CI: 6.64-9.61, p < 0.00001) and the mirodenafil group was also higher than placebo group in the changes from baseline for the IIEF EFD score (MD = 7.32, 95%CI: 5.56-9.07, p < 0.00001), respectively. The most common drug-related adverse events were flushing and headache (mirodenafil versus placebo: 15.8% versus 3.2%, 3.1% versus 0%; respectively). Conclusion: This meta-analysis suggested that mirodenafil is effective and well-tolerated therapy for ED.
    Full-text · Article · Nov 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Medical therapy is the preferred first-line approach in the management of lower urinary tract symptoms in men with benign prostatic hyperplasia. The magnitude of the improvement in lower urinary tract symptoms observed in response to combination therapy (alpha-blocker plus 5-alpha reductase inhibitors) does not approach that achieved with prostatectomy. Various drugs have been under consideration, including BXL628, lonidamine, and phosphodiesterase inhibitors, all of which have had unacceptable side effects. The gonadotropin-releasing hormone antagonist cetrorelix is associated with dose-dependent symptom improvement and reduction of prostate volume. Elucidating the mechanism for cetrorelix-mediated improvement in lower urinary tract symptoms will likely contribute to unraveling the pathophysiology of lower urinary tract symptoms in men.
    Article · Feb 2006
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