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Tadalafil significantly improves erectile function (EF), as assessed by
a variety of determinants of efficacy, including the following: the EF
domain of the International Index of Erectile Function (IIEF), which
classifies erectile function into five levels ranging from normal (26–30)
to severe (10) ; SEP Q2 and Q3 and the global assessment
questions (GAQ).
The SEP Q2 asks patients, “Were you able to insert your penis into your
partner’s vagina?” The SEP Q3 offers the key question, “Did your erection
last long enough for you to have successful intercourse?”The GAQ 1 and 2 are self administered at the end of the treatment period
during efficacy studies. For the GAQ 1, the patient is asked, “Has the
treatment you have been taking during the study improved your erections?”
GAQ then follows with Q2, “If ‘yes,’ has the treatment improved
your ability to engage in sexual activity?”. Using these assessment
tools, several studies have been conducted to determine the effectiveness
of tadalafil. Clinical trials have supported its efficacy and tolerability in a
broad population of men with ED.
The integrated analyses of randomized, double-blind, placebo-controlled
trials confirm the efficacy of tadalafil, particularly at doses of 10 and 20 mg,
according to a variety of end points. One integrated analysis
consisted of five trials including 1112 men, some with comorbidities of
hypertension or diabetes, and most with ED of more than 1-yr duration. After
a 4-wk, no-treatment baseline period, patients received fixed daily doses of
tadalafil (2.5–20 mg) or placebo in an at-home setting for the next 12 wk.
Patients were instructed to take the study medication as needed before sexual
intercourse, without restriction on food, alcohol use, or timing of sexual
activity. At the end point of these studies, the men responded to the GAQ,
which asked whether the treatment had improved their erections. Results
showed that the majority of men who received 10 or 20 mg of tadalafil felt
that treatment had improved their erections (p < 0.001) . Lower doses of tadalafil were less effective than 10 or 20 mg but still
elicited significantly more positive responses than placebo.
When EF was assessed by the EF domain of the IIEF, significant
improvement was observed at all doses of tadalafil (p < 0.001 vs placebo). Importantly, by the end point of the studies, normal erectile function
(defined by an IIEF EF domain score of 26 or more out of a possible 30)
was attained by 59% of men receiving 20 mg of tadalafil and 40% of men
receiving 10 mg of tadalafil, compared with 11% of those receiving placebo
(p < 0.001).
A subsequent analysis of 11 randomized, double-blind, 12-wk efficacy
trials conducted in more than 2000 patients indicated that tadalafil is effective
regardless of the baseline severity of ED. Thus, normal erectile function
was attained with 20 mg of tadalafil by 40% of men who had severe
ED at baseline (vs 3% for placebo control, p < 0.001).
In the integrated analysis of five trials, improved EF as measured by
SEP diary was accompanied by an increased number of successful
attempts at vaginal penetration (SEP Q2) and completion of intercourse
(SEP Q3). In this study, 57 to 80% of attempts at penetration were
successful in men receiving 5 to 20 mg of tadalafil, compared with 48%
in men receiving placebo (p < 0.001). More than twice the attempts at
intercourse were successful in men taking 20 mg of tadalafil than in men taking placebo (75% vs 32%, p < 0.001), with lower doses also being
effective.
In addition, the majority of men experienced successful intercourse after
taking their very first dose of tadalafil, 10 or 20 mg (56% and 67%, respectively,
vs 31% for placebo, p < 0.001). Moreover, even men with severe ED
experienced a 46 to 68% success rate for intercourse through the first four
doses of 10 or 20 mg of tadalafil (vs 20% for placebo, p < 0.001).
Overall, studies conducted in clinical settings that mimic real-life situations,
without restriction on food, alcohol, or timing of sexual activity,
show that tadalafil provides effective early treatment of ED irrespective of
its cause or severity. In addition, factors, such as age and ethnicity, do not
appear to influence the response to tadalafil. In the integrated analysis of
five randomized trials, the efficacy of tadalafil was similar in patients older
than 65 yr and in their younger counterparts. Tadalafil was similarly
effective in a study conducted in the United States and Puerto Rico, which
included men of diverse ethnic origin (73% white, 13% Hispanic, 13%
black, and 1% Asian) and in two primary US efficacy and safety trials
(78% white, 14% black, 7% Hispanic, and 1% other ethnicities).

PDE5 is found in the smooth muscle cells of systemic arteries and veins,
and inhibitors of this isoenzyme act as mild vasodilators. Through relaxation
of vascular smooth muscle, the hemodynamic effects of the PDE5
inhibitors can have major implications for the treatment of ED, especially
in patients with comorbid cardiovascular conditions, such as coronary
artery disease (CAD) and hypertension. Because patients with cardiovascular
disease (CVD) typically receive multiple drug regimens to control
angina, hypertension, and other cardiac conditions, potential drug interactions
between PDE5 inhibitors and agents used for management of these
conditions are particularly important.

Study results consistently show that tadalafil treatment has little effect
on systemic arterial pressure. This is supported by data reported on more
than 5700 subjects treated with tadalafil in more than 22 clinical trials. One study, conducted in 80 healthy subjects, showed that single
doses of 10 or 20 mg of tadalafil have only modest effects on systolic blood
pressure (SBP) or diastolic blood pressure (DBP). Continued dosing once a day for 10 d revealed no clinically significant
changes in standing or supine SBP or DBP or in heart rate. Additionally,
20 mg of tadalafil, administered to healthy male subjects produced no
significant difference compared with placebo in supine SBP and DBP
(difference in the mean maximal decrease of 1.6 and 0.8 mmHg, respectively)
and in standing SBP and DBP (difference in the mean maximal
decrease of 0.2 and 4.6 mmHg, respectively). In addition, there was no
significant effect on heart rate.
The modest hemodynamic effects of tadalafil in healthy subjects are
reflected in the analyses of five placebo-controlled studies in a general
population of men with ED and of one in men with comorbid diabetes.
Men with significant CVD (for example, history of myocardial infarction,
unstable angina, uncontrolled hypertension) were excluded from
these studies. Blood pressure and heart rate were measured at baseline
and at monthly intervals until the end of the 12-wk treatment period. No
clinically or statistically significant effects on SBP or DBP or heart rate
were observed over a range of doses of tadalafil (2.5–20 mg) compared
with placebo.