Download achieving treatment optimization with sildenafil citrate

ACHIEVING TREATMENT OPTIMIZATION WITH SILDENAFIL
CITRATE (VIAGRA®) IN PATIENTS WITH
ERECTILE DYSFUNCTION
ANDREW R. MCCULLOUGH, JAMES H. BARADA, AHMED FAWZY, ANDRE T. GUAY,
DIMITRIOS HATZICHRISTOU
AND
ABSTRACT
Since its approval in 1998, sildenafil citrate (Viagra) has been shown to be efficacious in ⬎100 clinical trials
involving ⬎8000 men with erectile dysfunction (ED). In clinical practice, however, many men do not continue
long-term use of sildenafil for a variety of reasons; thus, 6 different aspects of optimizing treatment with
sildenafil are described here. (1) Intercourse success rates, considered a reflection of real-world effectiveness, were assessed in 1276 patients with ED. Results indicated that the cumulative probability of achieving
intercourse success with sildenafil increased with the number of attempts, reaching a plateau after approximately 8 attempts. (2) A comprehensive disease management approach that included a medical history,
physical examination, educational material about ED, modifications of risk factors/lifestyle changes, and
counseling resulted in successful intercourse in 74% of 111 patients taking sildenafil. (3) A survey conducted
among primary care physicians revealed that almost 50% did not routinely question their patients about ED
symptoms, although it is known that most patients would prefer their physician to take the initiative. (4)
Overall, 55% of 137 men who were previously not successful with sildenafil became successful after
reeducation and counseling, which included information on patient and partner expectations, how to
properly take the drug, titration to maximum dose, and a minimum trial of 8 attempts for efficacy assessment. (5) Many men with ED have underlying comorbidities or take multiple medications that are risk factors
for ED. Controlling these risk factors in 521 men from a multispecialty clinic led to an overall intercourse
success rate of 82%; patients with multiple risk factors were less likely to have intercourse success than men
with only 1 risk factor. (6) Finally, treatment satisfaction is a pivotal factor in maintaining long-term ED
therapy. In an open-label trial, 82% of 443 subjects reported treatment satisfaction with sildenafil. In
summary, these findings highlight how important it is for physicians to take a more comprehensive, proactive
approach when treating men with ED, including control of risk factors, instructions on how to properly take
the drug, partner involvement, and follow-up visits. Using these recommended measures, most men with ED,
including those whose treatment was previously unsuccessful, can be treated successfully with
sildenafil. UROLOGY 60 (Suppl 2B): 28–38, 2002. © 2002, Elsevier Science Inc.
S
ince its approval in March 1998, the efficacy
and safety of sildenafil citrate (Viagra; Pfizer,
Inc, New York, NY) in treating erectile dysfunction
(ED) have been evaluated in clinical trials totaling
⬎11,000 patient-years.1 Overall, ⬎100 trials have
been completed or are ongoing, involving ⬎8000
men.2 Efficacy of sildenafil, as evaluated using a
global efficacy question (GEQ; improved ability to
have erections), varies depending on the etiology
and severity of ED and the comorbid conditions of
the patient population. For example, in men with a
broad spectrum of ED, sildenafil (50 and 100 mg)
improved erections in 77% to 84% of patients.3 In
specific patient populations, men with spinal cord
injury4,5 had high response rates (75% and 88%,
respectively), as did those with depression (90%).6
From the New York University Medical Center, New York, New
York, USA; Center for Male Sexual Health, Albany, New York,
USA; Urologic Institute of New Orleans, Gretna, Louisiana, USA;
Center for Sexual Function/Endocrinology, Lahey Clinic, Peabody, Massachusetts, USA; and Department of Urology, School of
Medicine and Centre for Sexual and Reproductive Health, Aristotle University of Thessaloniki, Thessaloniki, Greece
This supplement was funded by Pfizer Inc. Andrew R. McCullough, James H. Barada, Ahmed Fawzy, Andre T. Guay, and
Dimitrios Hatzichristou are paid consultants to, and study investigators funded by, Pfizer Inc.
Reprint requests: Andrew R. McCullough, MD, Department of
Urology, New York University Medical Center, 540 1st Avenue,
Sirball Building, Suite 10U, New York, New York 10016
28
© 2002, ELSEVIER SCIENCE INC.
ALL RIGHTS RESERVED
0090-4295/02/$22.00
PII S0090-4295(02)01688-6
In comparison, efficacy in men with diabetes
(65%)7 or after radical prostatectomy (45%)
tended to be lower.8,9
Current numbers indicate that approximately 30
million men in the United States are affected by
ED, with half of all men ⬎40 years of age experiencing some degree of ED.10 Unfortunately, most
men with ED (90%) remain undiagnosed because
they do not seek treatment for a condition from
which the overwhelming majority would benefit.11
ED can potentially be the first indication for other
underlying, serious diseases, and can have a significant effect on a patient’s quality of life. Because ED
and cardiovascular disease share many common
risk factors, men seeing a primary care physician
(PCP) for their ED should be screened for underlying cardiovascular disease. Conversely, men
seeking treatment and/or at high risk for hypertension, diabetes, depression, or other comorbidities
known to be associated with ED should be
screened for ED using, for example, the Sexual
Health Inventory for Men (SHIM).12 Many men are
reluctant to discuss ED with their physician. In
fact, a study in France involving ⬎7000 patients
with diabetes, hypertension, or both, demonstrated that, despite a high prevalence of ED,
⬎50% the patients had not been treated; however,
a large proportion of these patients wished to be
treated and wanted their physician to initiate a discussion on this topic.13
Since its approval in 1998, ⬎100 million prescriptions written by ⬎500,000 physicians have been
filled, with ⬎1 million new and/or refill prescriptions
dispensed each month for the past year.2 PCPs comprise the biggest group (64%) of prescribers, with
urologists, second (15%). However, urologists as a
specialty group wrote the most prescriptions per
month per physician (9.0), compared with PCPs,
who dispensed an average of 3.9 prescriptions per
month. Despite this high number of first-time prescriptions, patient behavior with respect to continued
drug use varies widely. Of patients tracked for 1 year
(March 2000 to February 2001) 52% filled a second
prescription during the 12-month period and 31%
filled ⬎7 prescriptions. The age group with the most
prescriptions (new and refill) was 50 to 59 years of
age (33%), followed by 60 to 69 (25%) and 40 to 49
years of age (21%).2
Ideally, a prescription refill rate similar to the clinical efficacy rate of 70% might be expected. However,
clinical trials are designed to demonstrate efficacy
and do not necessarily reflect real-world considerations. For example, in clinical trials, (1) patients are
more motivated, (2) patients and partners are better
educated because both have to sign an informed consent form, (3) medication is free of cost, and (4) follow-up/reeducation are provided by physicians and
research staff who are highly knowledgeable in treatUROLOGY 60 (Supplement 2B), August 30, 2002
ing ED. On the other hand, failure to continue using
the drug on a long-term basis could be caused by
numerous reasons including: (1) disappointment
with the initial results, (2) concern about safety issues, (3) being bothered by or misunderstanding side
effects, (4) relationship problems (their partner may
not be interested in resuming sexual activity), (5) the
cost of the medication, or (6) gradual loss of efficacy
caused by worsening underlying medical conditions.
Proper instructions by physicians prescribing sildenafil to their patients on how to use the drug
appear to play an important role in treatment satisfaction, outcome, and continued use. The level of
understanding the treating physician has of ED,
how comfortable they are in initiating treatment
for ED, how much time is spent educating a patient, how much, if any, follow-up treatment is
provided, and whether patients are referred to a
specialist (immediately, or only after sildenafil
fails) are all vital for treatment success. Moreover,
the involvement and/or education of the patient’s
partner is paramount to success because patients
seeking treatment for ED may not have been sexually active for long periods of time, and their partners may not be immediately receptive to resuming
sexual activity. The data presented in this article
show the benefit of proper patient education and
follow-up treatment by the physician, and the success that can result with persistent use of sildenafil,
even if the initial attempts fail.
METHODS
Many different approaches have been taken to assess and
improve success of sildenafil treatment for ED, including 6
studies described below.
ASSESSMENT OF INTERCOURSE SUCCESS RATES
Measurement of intercourse success is considered representative of real-world effectiveness. Thus, intercourse success
rates were assessed by examining data obtained from event
logs of 1276 patients with ED who were enrolled in 6 prospective, double-blind, placebo-controlled, flexible-dose studies
from 1996 to 1998. Men taking sildenafil (n ⫽ 654) or placebo
(n ⫽ 622) were stratified by ED severity based on scores from
the erectile function (EF) domain of the International Index of
Erectile Function (IIEF)14,15: no ED, EF domain score 26 to
30; mild ED, 22 to 25; mild-to-moderate ED, 17 to 21; moderate ED, 11 to 16; severe ED, 1 to 10.
Event log questions included: (1) Was the study medication
taken? (2) Did you have any sexual stimulation? (3) Did you
have successful intercourse? Unlike many studies using the
IIEF, which relies on 4-week patient recall, this study used
immediate recall of every sexual experience with sildenafil.
DISEASE MANAGEMENT APPROACH
This was a comprehensive disease management program
that included several different elements, such as a complete
medical history and physical examination, educational material on ED and on all available treatment options, modifications or risk factors/lifestyle changes as appropriate, and
initiation of sexual counseling when clinically appropriate.
29
PCPs have taken on an increasingly important role in the
management of ED, and how well that task is handled is vital
for treatment success. A 9-question survey was distributed to
PCPs attending scientific meetings between April and December 1998. Overall, 1634 physicians (46% family physicians,
32% internists, and 22% in other specialties) were surveyed on
how they treated their patients with ED.16
using nitrates, or who had failed a cardiac stress test were
excluded from this study.
Medication and Lifestyle Modification. Medical and drug-use
histories were retrieved from the clinical database. Patients
using medications believed to interfere with sexual functioning were switched to an alternative drug. For example,
␤-blockers (eg, metoprolol or propanolol) believed to aggravate sexual dysfunction were replaced with atenolol. Similarly, patients with hypertension were considered for a switch
to an angiotensin-converting enzyme inhibitor or an angiotensin-receptor antagonist, and patients with hyperlipidemia who
were taking gemfibrozil were switched to a statin.18
Smokers were encouraged to stop smoking or to reduce
their cigarette intake. Patients were encouraged to limit alcohol intake to 1 drink per day on those days that sildenafil was
used and to ⱕ2 drinks per day on other days.
Hormonal Assessment. Because hypogonadism may be a contributing factor in causing ED, patients whose profiles indicated a possibility of hypogonadism were evaluated for serum
testosterone levels; if found to be below age-appropriate levels, patients were given a testosterone supplement or had their
endogenous testosterone levels increased using the fertility
drug clomiphene citrate. Men with known hypogonadism
were treated with testosterone replacement therapy for 3
months; if their ED did not resolve, sildenafil treatment was
initiated. A small group of patients (n ⫽ 44) received sildenafil
treatment before a diagnosis of hypogonadism was made. Sildenafil efficacy in these men was compared with those men
with hypogonadism who had the benefit of a 3-month testosterone therapy.
Patients received an initial 50-mg dose of sildenafil, which
could be adjusted to 25 mg or 100 mg based on efficacy and
tolerability, and recorded the number of successful intercourse attempts for a period of 6 to 8 weeks. Success was
defined as an erection rigid enough for vaginal penetration and
of long enough duration to reach ejaculation. Adverse events
were also noted throughout this time.
REEDUCATION OF MEN WHO WERE INITIALLY
SILDENAFIL NONRESPONDERS
ASSESSMENT OF TREATMENT SATISFACTION WITH
SILDENAFIL
Consecutive patients who visited a urology clinic were enrolled in a goal-oriented disease management program for up
to 18 months. At the initial visit, a complete medical history
was taken and a physical examination was performed. When
clinically indicated, a male hormone panel, sequential multiple analyzer–7, and penile Doppler examination were also performed. Major inclusion criteria were: male patients ⬎18
years of age with a clinical diagnosis of ED of any etiology, who
visited the clinic between April 1998 and December 1998.
Patients with contraindications for the use of sildenafil were
not eligible. A starting dose of 50-mg sildenafil was prescribed,
and patients with a partial response or no response to sildenafil at the 1-month follow-up visit were given the 100-mg dose.
At subsequent follow-up visits (3, 6, and 12 months), those
patients who failed to respond to the 100-mg dose were
switched to other treatment options, based on patient and
partner preference. EF was assessed using question (Q)3
(achieving an erection) and Q4 (maintaining an erection)
from the IIEF, which were rated on a 5-point scale ranging
from 1 (almost never/never) to 5 (almost always/always), with
a score of 0 corresponding to no sexual activity. Responders
were classified based on the treating physician’s clinical assessment and the patient’s responses to questions Q3 and Q4
of the IIEF. Responses were classified as successful (an erection sufficient for penetration), partial (an erection not sufficient for penetration), and failure (no erection).
PRACTICE PATTERNS OF PRIMARY CARE PHYSICIANS IN
ERECTILE DYSFUNCTION MANAGEMENT
A retrospective chart review of men exposed to sildenafil
therapy by their PCP for the treatment of ED over a 22-month
period was used to identify 137 men who had been unsuccessful with sildenafil. Patients received a review of their referral
chart; a physician interview; a patient recall questionnaire; the
IIEF questionnaire before and after therapy; and education on
ED, sildenafil, patient expectations, and other therapy options. Patient recall of the evaluation and education was assessed, and dose titration was obtained from the referring
PCP. Patients without contraindications were offered a second
trial of sildenafil after intensive education, including titration
to the 100-mg dose for those who had not previously done so.
Therapy outcome was measured using Q3/Q4 from the IIEF
and a GEQ. A minimum trial of 8 attempts at the final dose was
used for efficacy assessment.17
CONTROL OF ASSOCIATED RISK FACTORS
Many men with ED have underlying comorbidities that are
risk factors for ED. Controlling these risk factors with medication and/or lifestyle changes can improve the chance of success with sildenafil treatment. This was an open-label study of
521 patients with ED (based on self-assessment) in a multispecialty clinic.9 Associated risk factors, such as hypertension,
hypogonadism, and/or use of multiple medications were managed by lifestyle modification/medication before ED treatment
with sildenafil. Patients with ED for ⱖ6 months and an intercourse failure rate of ⱖ50% were eligible for inclusion. Patients who had previously used sildenafil, were concurrently
30
Treatment satisfaction by both patient and partner can play
a critical role in maintaining long-term therapy for ED. To
assess this, a multicenter, open-label, single-treatment study
with flexible dosing was performed. There were 2 phases: an
8-week primary phase, followed by a 28-week extension
phase. Only data from the 8-week phase are reported here.
Overall, 443 subjects were enrolled at 77 sites: 235 who had
not been receiving treatment for their ED before this study
(n ⫽ 125 aged ⱕ60 years; n ⫽ 110 ⬎60 years) and 208 who
had received ED treatment other than sildenafil (yohimbine,
intracavernosal [IC] alprostadil, IC phentolamine, and/or papaverine, vacuum device) before entering the study (n ⫽ 107
aged ⱕ60 years; n ⫽ 101 ⬎60 years).
Primary efficacy was analyzed after 8 weeks using the 11-item
Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS).19 Answers are scored from a range of 0 to 5; subsequently,
for each patient, the average of scores from questions 1 to 11 was
multiplied by 25 to give a total score ranging from 0 to 100. This
EDITS index score was used as the primary efficacy variable, and
treatment satisfaction was defined as a score ⱖ50.
Secondary efficacy assessments included 3 GEQs (GEQ1,
improved erections; GEQ2, improved ability for sexual intercourse; GEQ3, frequency of erection that allowed satisfactory
intercourse) and 2 questions from the SHIM, a shortened,
5-item version of the IIEF (Q4, achieving an erection; Q5,
maintaining an erection). Responses to GEQs 1 and 2 were
yes/no; responses to GEQ3, Q4, and Q5 were rated on a
5-point scale: 1 ⫽ almost never/never to 5 ⫽ almost always/
always, 0 ⫽ did not attempt intercourse.
UROLOGY 60 (Supplement 2B), August 30, 2002
FIGURE 1. Distribution of patients by erectile dysfunction severity. ED ⫽ erectile dysfunction; EF ⫽ erectile function.
RESULTS
ASSESSMENT OF INTERCOURSE SUCCESS RATES
Distribution of patients by ED severity is shown
in Figure 1. The cumulative probability of achieving intercourse success with sildenafil increased
with the number of attempts (54% and 64% for the
first and second attempt, respectively) and reached
a plateau of 86% (Figure 2). A similar pattern was
seen in men with mild-to-moderate (n ⫽ 372) or
severe ED (n ⫽ 248) on sildenafil who reached a
cumulative probability of 85% and 65%, respectively (Figure 2).
In most patients, success occurred with the
50-mg dose. In all, 46% of attempts with sildenafil
(vs 12% with placebo) resulted in successful intercourse 90% of the time, whereas 80% of attempts
with sildenafil (vs 41% with placebo) resulted in
successful intercourse ⱖ50% of the time. Thus, the
therapeutic success rate of sildenafil was sustained.
DISEASE MANAGEMENT APPROACH
A total of 200 patients were screened, 111 patients were enrolled, and 96 patients completed the
study. Overall, 60 of 111 (54%) patients reported a
“successful response” to a 50-mg dose of sildenafil
at the 1-month visit (patients had been instructed
to have 4 to 6 attempts; Figure 3). Of those patients
who reported a “partial response” at the 1-month
visit (n ⫽ 32), ⬎50% (n ⫽ 19) became successful
with a higher dose of sildenafil, and 2 patients reported success after switching to intraurethral alprostadil suppositories.
By the end of the study, 74% (82 of 111) of patients who received 50 mg or 100 mg of sildenafil
reported successful intercourse (Figure 3). Of
those patients who did not respond to an increased
dose of sildenafil (n ⫽ 29), 17% (5 of 29) became
UROLOGY 60 (Supplement 2B), August 30, 2002
successful after switching to a different treatment
modality (intraurethral alprostadil suppositories,
n ⫽ 2; IC injection, n ⫽ 2; vacuum pump, n ⫽ 1),
and 52% (15 of 29) opted not to switch treatments
and discontinued. Responses to Q3 and Q4 from
the IIEF are shown in Figure 4.
PRACTICE PATTERNS OF PRIMARY CARE PHYSICIANS IN
ERECTILE DYSFUNCTION MANAGEMENT
This survey showed that less than half (45%) of
physicians routinely questioned their patients
about ED-related symptoms. Most PCPs relied on a
detailed sexual history (71%) and a complete medical history and physical examination (74%) to
make an ED diagnosis, whereas 53% and 36% used
routine laboratory analysis and serum testosterone/luteinizing hormone/prolactin determinations, respectively, as the initial diagnostic tests.
For treatment of ED, most physicians relied on lifestyle changes (70%), sexual counseling (57%), sildenafil prescriptions (60%), and hormone therapy
(25%). To a lesser degree, PCPs prescribed vacuum
devices (17%), intraurethral alprostadil suppositories
(15%), and IC injection therapy (9%).16
REEDUCATION OF MEN WHO WERE INITIALLY
SILDENAFIL NONRESPONDERS
Data from 137 consecutive men exposed to sildenafil, referred by 27 different PCPs, were analyzed between August 1998 and July 2000 (22 months).
Complete follow-up data were available for 114 of
137 men (83%). Overall, 36% of men recalled PCP
discussion of side effects, food/alcohol effects (34%),
and patient-partner expectation of therapy (21%).
More than half (55%) were referred after a maximal
dose of 50 mg and/or a trial of ⬍5 attempts. In all,
23% then elected no further therapy or therapy
31
FIGURE 2. Intercourse success rates, as determined from event log data, in men with erectile dysfunction taking
sildenafil (top). Intercourse success rates in men stratified by erectile dysfunction severity (bottom).
change, and 3 patients had a nitrate-use contraindication. The remaining 85 men were reeducated in
sildenafil use and expectations, and 89% of those initiated therapy at the 100-mg dose. Adverse events or
partner discord caused 9 patients not to complete the
rechallenge (Figure 5). Altogether, 41 of 76 (54%) of
those completing the trial were responders as judged
from Q3/Q4 of the IIEF and the GEQ. Patients with
diabetes, taking multiple hypertensive agents, and active smokers were more likely to be nonresponders. A
total of 13 of 35 (37%) nonresponders went on to
successful therapy with other treatment modalities
that included IC injections and penile prostheses
(Table I).
CONTROL OF ASSOCIATED RISK FACTORS
Patients (median age, 59 years) who had modified their associated risk factors had an overall suc32
cess rate of 82% (defined as an erection rigid
enough for vaginal penetration and of long enough
duration to reach ejaculation); success at every intercourse attempt occurred in 77% of patients. The
success rate for those men with concomitant medical conditions ranged from 43% in patients having
undergone nerve-sparing prostatectomy, to 85% in
hypogonadal patients receiving testosterone treatment, patients with neurologic disease, and those
abusing alcohol (Figure 6). The success rate was
second highest in patients with hypertension
(83%), followed by smokers (80%), those taking
multiple medications (77%), and those with
asymptomatic coronary artery disease (71%). Patients with multiple risk factors, such as those with
hypertension and diabetes (n ⫽ 43), had a higher
percentage of intercourse failures (35%) compared
with men who had only 1 risk factor.
Efficacy in the subgroup of patients with hypoUROLOGY 60 (Supplement 2B), August 30, 2002
FIGURE 3. Patient disposition in a disease management program.
gonadism and known low levels of free testosterone (n ⫽ 44) was compared with a control group of
44 men with normal levels of free testosterone
(ⱖ11 pg/mL) and similar concomitant risk factors.
Men with slightly low testosterone levels (n ⫽ 33;
10.6 pg/mL) reported that 75% of all intercourse
attempts with sildenafil were successful. Men with
moderately low testosterone levels (n ⫽ 7;
8.1 pg/mL) reported a success rate of ⬍75%,
whereas men with severely low testosterone levels
(n ⫽ 4; 7.4 pg/mL) did not respond to sildenafil at
all. Overall, 18% of all patients were sildenafil nonresponders (defined as ⬎75% of intercourse attempts failing), despite attempts to control associated risk factors.
ASSESSMENT OF TREATMENT SATISFACTION WITH
SILDENAFIL
After 8 weeks of dosing with 25-, 50-, or 100-mg
doses of sildenafil, 82% of patients responding to the
EDITS questionnaire were satisfied with their treatment, as defined by a combined EDITS score of ⱖ50.
Estimated satisfaction rates were similar in men preUROLOGY 60 (Supplement 2B), August 30, 2002
viously untreated (83%) and previously treated
(84%) for ED, and were slightly higher in younger
than in older men, regardless of the kind of treatment
received before this study (86% vs 80%).
Responses to the SHIM indicated an improvement in the ability to achieve and maintain an erection and in overall satisfaction with sexual intercourse during the previous 8 weeks (Figure 7).
Similarly, efficacy as measured using 3 GEQs demonstrated that sildenafil was efficacious, regardless
of the age of the patient or whether they had received prior treatment for their ED (Table II).
COMMENT
Because more men are seeking treatment for
their ED, physicians, especially PCPs, are increasingly more involved in the decision-making process about evaluation and treatment of these patients.16 Surveys have shown that overall treatment
success and long-term use of sildenafil are lower
when prescribed by PCPs compared with specialists.20 Likely reasons include differing patient populations and expectations, and insufficient PCP
33
FIGURE 4. Efficacy results in a disease management program. Baseline and end-of-treatment (EOT) scores for
International Index of Erectile Function question (Q)3 and Q4. EOT scores are patient responses to Q3 and Q4 at
the stage they reached “success” (ie, 50 mg sildenafil, 100 mg sildenafil, switch to another treatment modality).
knowledge to be able to diagnose, educate, and
treat patients with ED. Considering that PCPs
comprise the biggest group of prescribers, it is clear
that better education on sexual health is needed for
this group of healthcare providers. In general,
PCPs and other healthcare providers dealing with
the increasing incidence of ED face 4 major issues:
(1) realizing the importance of identifying and
treating patients with ED, (2) increasing the effectiveness of this process, (3) providing adequate patient education on the use of sildenafil, and (4)
providing proper patient follow-up.
THE IMPORTANCE OF IDENTIFICATION AND TREATMENT
OF PATIENTS WITH ERECTILE DYSFUNCTION
Because ED shares a number of risk factors with
cardiovascular disease, and may be the first indication and possibly a surrogate marker for underlying cardiovascular disease, screening for ED will
likely identify high-risk patients and allow earlier
detection and treatment of serious diseases, such as
hypertension, diabetes, and dyslipidemia (eg, cardiovascular disease, peripheral vascular disease).
By modifying these risk factors, subsequent treatment of ED has a better chance of success. In addition, ED can have a major negative impact on selfesteem and quality of life of both the patient and
his partner. ED can lead to depression, and the use
34
of antidepressant drugs can in turn aggravate ED.
ED that may develop as a result of medications
used to treat chronic conditions, such as hypertension, diabetes, dyslipidemia, and depression, can
be treated successfully with sildenafil, which may
result in improved treatment compliance for
chronic, yet potentially life-threatening diseases.
EFFECTIVENESS OF IDENTIFICATION AND TREATMENT OF
PATIENTS WITH ERECTILE DYSFUNCTION
With approximately 90% of men with ED remaining undiagnosed and untreated, changes in
the way healthcare providers deal with this issue
are needed. Perceptions of ED therapy appear to be
different between PCPs and specialists/urologists,
with treatment outcomes less favorable in the
former group. PCPs are less likely to screen at-risk
patients and to identify and refer for treatment failures.16 Although surveys have shown that patients
clearly wish their physician to bring up the subject
of sexual health,13 embarrassment of both parties
(patient and physician) often prevents an open discussion on this topic. PCPs might also be hampered by time constraints, and typically, they may
not educate patients on all available treatment options. Specialists, on the other hand, often perform
a more detailed diagnostic evaluation, take a more
goal-oriented disease management approach, and
UROLOGY 60 (Supplement 2B), August 30, 2002
FIGURE 5. Patient disposition of initial sildenafil nonresponders. AE ⫽ adverse event; GEQ ⫽ global efficacy
question; IIEF ⫽ International Index of Erectile Function.
TABLE I. Initial sildenafil nonresponders: efficacy after patient
reeducation
GEQ1, %
GEQ2, %
Mean number of attempts
before first success
(range)
IIEF Q3, mean score
IIEF Q4, mean score
Yes
No
59
52
41
48
3.1 (1–9)
Baseline
12 Weeks
1.6
1.4
3.4
3.1
GEQ ⫽ global efficacy question; IIEF ⫽ International Index of Erectile Function; Q ⫽ question.
tend to recognize and address treatment failures
early. The use of the SHIM, a brief, validated instrument, can be very helpful in identifying patients
with ED and can be used to document EF before
prescribing agents that may contribute to ED (eg,
antihypertensives, lipid-lowering agents, antidepressants) and should be used routinely in all men
UROLOGY 60 (Supplement 2B), August 30, 2002
with cardiovascular, metabolic, or psychiatric disease.12
PROPER EDUCATION ON THE USE OF SILDENAFIL
Physicians should better educate their patients on
the use of sildenafil. Increasingly, sildenafil is the
treatment of choice that will be offered to a patient,
35
FIGURE 6. Sildenafil efficacy in patients with risk factors or concomitant conditions (percent success). Partial
success was determined only in the HYP⫺T group. Proportions of successful versus unsuccessful patients for each
condition were compared using binomial tests of independent proportions. Significant difference at P ⱕ0.05.
A-CAD ⫽ asymptomatic coronary artery disease; ALC ⫽ alcohol abuse; ASMA ⫽ asthma; DM ⫽ diabetes mellitus;
DM⫹NP ⫽ diabetes mellitus plus neuropathy; HYP⫹T ⫽ hypogonadism plus testosterone treatment; HYP⫺T ⫽
hypogonadism without testosterone treatment; HTN ⫽ hypertension; HTN⫹DM ⫽ hypertension plus diabetes
mellitus; MM ⫽ multiple medications; ND ⫽ neurological disease; PRO ⫽ nerve-sparing prostatectomy; PFIB ⫽
penile fibrosis; PVD ⫽ peripheral vascular disease; TOB ⫽ tobacco abuse; TURP ⫽ transurethral resection of the
prostate.
and if proper instructions are not given and immediate intercourse success is not achieved, men are
less likely to continue their trial with sildenafil and
may potentially give up on ED treatments entirely.
Thus, when educating patients, the physician
should emphasize the following: (1) the need for
sexual stimulation, (2) the proper timing of when
to take the drug (including its relation to meals and
the types of food eaten), (3) the importance of dose
titration when lower doses are not effective, and
(4) the need for patience (eg, taking the drug on
several occasions to provide adequate opportunity
for success). In addition, patients should understand that although sildenafil is to be taken approximately 30 to 60 minutes before intercourse, its
effect can last approximately 4 hours, allowing
more spontaneous use. However, the therapeutic
effect can be delayed and/or compromised by a
high-fat meal, smoking, and/or excessive alcohol
intake during the hours preceding sexual activity.
THE IMPORTANCE OF FOLLOW-UP VISITS
If men are unsuccessful with sildenafil, the physician should carefully evaluate the following: (1)
36
has the patient had sufficient exposure to the drug
(eg, were there more than a couple of attempts at
intercourse, was there adequate dose titration), (2)
has the drug been taken appropriately (eg, was
there sexual stimulation), and (3) have risk factors
been modified and underlying diseases been
treated. Men who have previously failed with sildenafil can become successful with reeducation
and/or dose escalation. Finally, whether or not
men have the support of their partners can be the
deciding factor for treatment success. A study by
Lewis et al.21 has shown that involvement of the
partner when making treatment decisions is associated with higher treatment satisfaction in men
and their partners.
After ED diagnosis with the SHIM, treatment
progress can be monitored during regular follow-up visits to the treating physician.19 If all of the
above issues have been addressed and sildenafil
treatment still fails, the patient may have a more
severe underlying associated condition, such as peripheral vascular disease or hypogonadism. Therefore, inappropriate follow-up treatment/assessment by the physician can lead not only to
UROLOGY 60 (Supplement 2B), August 30, 2002
FIGURE 7. Responses to question 4 (Q4; ability to maintain an erection) and Q5 (ability to have satisfactory sexual
intercourse) from the Sexual Health Inventory for Men questionnaire. Responses were rated from 1 (most positive)
to 5 (most negative). Thus, a decrease in score represents an improvement in response. EOT ⫽ end of treatment.
TABLE II. Treatment satisfaction study: efficacy after 8 weeks
Previously Untreated for ED
GEQ1, % yes
GEQ2, % yes
GEQ3, mean
Previously Treated for ED
<60 yr
(n ⴝ 122)
>60 yr
(n ⴝ 108)
Total
(n ⴝ 230)
<60 yr
(n ⴝ 105)
>60 yr
(n ⴝ 98)
Total
(n ⴝ 203)
91.0
90.0
4.2
85.2
82.4
3.7
88.3
86.4
3.9
91.4
85.7
4.0
83.7
83.3
3.6
87.7
84.6
3.8
ED ⫽ erectile dysfunction; GEQ ⫽ global efficacy question.
inadequate treatment for ED, but also to potentially serious comorbidities being undiagnosed
and/or untreated.
RECOMMENDATIONS FOR SILDENAFIL
TREATMENT OPTIMIZATION
The treatment guidelines below should aid physicians in better identifying and treating patients
with ED and help ensure continued treatment success.
EVALUATION AND TREATMENT CONSIDERATIONS
● PCPs should screen their patients for ED because ED may be the first indication and a possible
surrogate marker of more generalized peripheral
vascular, cardiovascular, or metabolic disease. A
medical history (including a sexual history) should
be taken, and a focused physical examination
should be performed.
● Control medical risk factors, either before or at
the time of issuing a sildenafil prescription: (1)
encourage discontinuation of smoking and moderation in alcohol consumption (ie, no smoking or
drinking in the hours preceding sildenafil use); (2)
control hyperlipidemia, hypertension, and diabeUROLOGY 60 (Supplement 2B), August 30, 2002
tes; (3) when medically appropriate, consider
switching patients from existing medications that
may aggravate ED to others known to have less of
an effect on EF; and (4) treat hypogonadism as
appropriate.
● Include the patient’s partner in the treatment
decision-making process whenever possible, especially if ED has been present for a long time.
● Refer to sexual counseling and/or specialist
care whenever appropriate.
PHYSICIAN INSTRUCTIONS AND PATIENT EDUCATION
● Emphasize the need for sexual stimulation.
● Instruct the patient about titrating appropriately. For example, counsel patients to try a
100-mg dose of sildenafil if the 50-mg dose is well
tolerated but does not provide adequate efficacy, or
decrease to 25 mg if appropriate.
● Instruct the patient about timing—take the
drug anytime before or after a meal, approximately
30 to 60 minutes before sexual activity and no
more than once a day; however, if a faster onset is
desired, it should be taken on an empty stomach
(or at least not after a high-fat meal); however, the
therapeutic window for effectiveness covers ap37
proximately a 4-hour period. Even if intercourse
does not occur within the first hour after taking
sildenafil, many patients do not realize that they
can still have successful intercourse for several
hours thereafter, allowing more spontaneity.
● Explain that excessive use of alcohol should be
avoided, as it can have a negative effect on EF;
however, there are no safety concerns about the
concomitant use of alcohol and sildenafil.
● Inform patients that although most responses
occur within the first 1 to 2 doses, it may take up to
7 to 8 attempts (including titration to the correct
dose) for some patients before they achieve intercourse success; patients need to be encouraged not
to give up before an adequate number of attempts
have been tried, using the maximum tolerated dose
along with adequate sexual stimulation. The first
few attempts at intercourse may be very emotionally charged and anxiety-producing for both patient and partner, especially if patients have not
been sexually active for a long time.
FOLLOW-UP ASSESSMENT, EFFICACY, AND SIDE EFFECTS
● Schedule follow-up visits at regular intervals
to assess treatment progress. This is essential for
the best possible treatment outcome, especially if
concomitant diseases are present that could
worsen over time, possibly affecting treatment efficacy. Lack of follow-up assessment/treatment
may deprive the patient of an effective therapy and
may fail to uncover more serious comorbid conditions.
● Discuss side effects with the patient. The most
common side effects of sildenafil are headache, facial flushing, and dyspepsia. Less commonly, nasal
congestion, bluish vision, blurred vision, or sensitivity to light may occur. Most of these side effects
have been mild to moderate and transient. In clinical trials, treatment discontinuation because of
side effects has been low.1,22
● Understand that the most important consideration for patients taking sildenafil seems to be efficacy, not side effects. Thus, education on how to
optimize efficacy and treatment satisfaction is a vital part of a healthcare provider’s task.
● Ensure that patients taking either long- or
short-acting nitrates do not use sildenafil.
ACKNOWLEDGMENT: We thank Linda Merkel, Ph.D. for help
in the preparation of the manuscript.
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