Download Frailty and treatments for benign prostatic hyperplasia

■ THERAPY MANAGEMENT
Frailty and treatments for
benign prostatic hyperplasia
STEVE CHAPLIN
Many older men are likely
to have lower urinary
tract symptoms (LUTS)
associated with benign
prostatic hyperplasia
(BPH). Having LUTS can
increase the risk of frailty,
and the drugs used to
treat the symptoms can
exacerbate the problem.
This article examines
these risks and how they
can be reduced.
Syndrome
Examples
Falls
Collapse, legs gave way, “found lying on floor”
Immobility
Sudden change in mobility, “gone off legs”, “stuck
in toilet”
Delirium
Acute confusion, “muddledness”, sudden worsening
of confusion in someone with previous dementia or
known memory loss
Incontinence
Change in continence – new onset or worsening of
urinary or faecal incontinence
Susceptibility to sideeffects of medication
Confusion with codeine, hypotension with
antidepressants
Table 1. Frailty syndromes4
F
railty is “a state of increased vulnerability to poor resolution of homeostasis
following a stress, which increases the
risk of adverse outcomes including falls,
delirium and disability.”1 Depending on
how this is measured, the prevalence of
frailty among men over 64 years old has
been estimated at 4–19 per cent, with
rates doubling after age 80–85 years.2,3
Fit for Frailty, published by the British
Geriatrics Society, the Royal College of
General Practitioners and Age UK, set out
best practice for caring for older people
living with frailty.4 Frailty is not necessarily associated with older age, disability
or ill health but it should be suspected
when a person presents with a frailty
syndrome (see Table 1). Of these, the
adverse effects of medication are a particular concern.
Polypharmacy is recognised as a risk
factor for frailty.4 It is more prevalent with
increasing age: one in six people in their
70s and almost one in four of those aged
over 80 years may be prescribed 10 or
more medicines. 5 The risk of adverse
effects leading to hospital admission
and drug interactions increases with the
number of medicines prescribed.5-7
42 ❚ Prescriber January 2017
Benign prostatic hyperplasia
and frailty
Benign prostatic hyperplasia (BPH), as
indicated by lower urinary tract symptoms
(LUTS) not likely to have an alternative
cause, is increasingly common with age
and, in one 2005 UK study, was reported
by more than 30 per cent of men aged
over 80 years (see Figure 1).8
Having LUTS increases the risk of
frailty. Compared with men with mild
symptoms, having moderate symptoms
increased the risk of a fall by 11 per
cent and of two falls by 21 per cent; the
increased risks for severe symptoms
were 33 and 63 per cent respectively.9
The symptoms most strongly predicting falls were urinary urgency, difficulty
initiating urination and nocturia, which
is at least partially consistent with the
hypothesis that the increased risk may
be linked with hasty visits to the toilet at
night.
Drug treatment for BPH
Medication review with older people
is recommended to reduce the treatment burden and the risk of adverse
events.10-12 Treatment for BPH improves
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BPH and frailty
400
350
Cases of LUTS
300
250
200
150
100
50
0
45505560 657075808590
Age (years)
Figure 1. Mean incidence (new cases per 1000 observed years) (red line) and prevalence
(cases per 1000 patients) (blue line) of lower urinary tract symptoms (LUTS) suggestive of
benign prostatic hyperplasia in UK primary care8
bothersome symptoms and may therefore reduce some of the risks posed by
frailty but it may also be associated with
troublesome adverse effects, drug interactions and longer term complications.
Balancing benefit and risk in people with
frailty means making a careful choice of
pharmacological class and agents within
a class.
The options for drug treatment for
bothersome voiding symptoms associated with BPH are an alpha-blocker
(alfuzosin, doxazosin, tamsulosin, terazosin) and/or a 5-alpha reductase inhibitor (5-ARI; dutasteride, finasteride) (see
Table 2).13 (An anticholinergic agent may
additionally be considered for men who
have storage symptoms after treatment
with an alpha-blocker.) The risk posed
by anticholinergic drugs in older frail
people is well recognised but the potential problems of the more widely used
alpha-blockers and 5-ARIs have received
less attention. In the 2005 UK study,
about 20 per cent of men with LUTS were
using medication, of which alpha-blockers accounted for about three-quarters
and 5-ARIs for one-quarter.8
Alpha-blockers
The alpha-blockers are preferred for men
who have moderate to severe symptoms
but have smaller prostate volumes.
These agents are vasodilators but their
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selectivity for receptor subtypes differs
and this influences their impact on blood
pressure. Patients prescribed alfuzosin
or terazosin should be warned of the risk
of profound first-dose hypotension; tamsulosin is generally considered to have
least effect on blood pressure.14
All alpha-blockers pose a risk to people with frailty. They lower blood pressure
and are associated with hypotension,
dizziness and syncope, and an increased
risk of falls, fractures and admission
to hospital.15-18 The risk appears to be
greatest during the first eight weeks of
treatment and then diminishes, but it
persists during maintenance use17,18 and
recurs when restarting treatment.18
A consensus panel concluded that
tamsulosin offered questionable ben-
l THERAPY MANAGEMENT ■
efits in the treatment of older people
with LUTS and that other alpha-blockers should be avoided, largely because
of lack of evidence of efficacy in this
age group and safety concerns. 19 In a
meta-analysis of 124 clinical trials involving a total of 58,500 men, terazosin was
associated with a significantly greater
risk of adverse effects and treatment discontinuation due to adverse effects than
tamsulosin or alfuzosin, which were not
significantly different from one another.20
Treatment with alpha-blockers should
be reviewed after four to six weeks and
then every 6–12 months. 13 Clinically,
the most important drug interaction
with alpha-blockers is the risk of additive hypotension. This can occur with
most classes of drugs prescribed for
cardiovascular disorders and some centrally-acting drugs such as tricyclic antidepressants (SSRIs are an alternative).
Phosphodiesterase type 5 (PDE5) inhibitors, eg sildenafil, which are vasodilators,
may increase the risk of hypotension and
should be used at the lowest possible
dose; combinations with doxazosin and
terazosin are not recommended.21
5-alpha reductase inhibitors
The 5-ARIs finasteride and dutasteride
are preferred to the alpha-blockers in
men with large prostate volume; they
relieve symptoms more slowly (taking up
to six months) but may reduce BPH progression.22 They are well tolerated, have
few contraindications and a low risk of
drug interactions but they are associated
with sexual dysfunction (see Table 3).23-25
The 5-ARIs are not associated with
an increased risk of fracture overall, or
Symptoms
Treatment
Moderate to severe LUTS
Alpha-blocker
LUTS plus prostate >30g or PSA
>1.4ng/ml, and who are at high risk of
progression
5-alpha reductase inhibitor
Bothersome moderate to severe LUTS
and prostate >30g or PSA >1.4ng/ml
Alpha-blocker plus 5-alpha reductase
inhibitor
Storage symptoms after treatment with
an alpha-blocker
Consider adding an anticholinergic
agent
Table 2. Treatments recommended by NICE for bothersome lower urinary tract symptoms (LUTS)13
Prescriber January 2017 ❚ 43
■ THERAPY MANAGEMENT l BPH and frailty
Drug-related adverse events
occurring in ≥1 subject
Combination
(n=1610) %
Dutasteride
(n=1623) %
Tamsulosin
(n=1611) %
Erectile dysfunction
Retrograde ejaculation
Decreased libido
Ejaculation failure
Semen volume decreased
Loss of libido
Dizziness
Gynaecomastia
Nipple pain
Breast tenderness
9
4
4
3
2
2
2
2
1
1
7
<1
3
<1
<1
1
<1
2
<1
1
5
1
2
<1
<1
1
2
<1
<1
<1
Table 3. Adverse effects associated with the 5-alpha reductase inhibitor dutasteride and the
alpha-blocker tamsulosin, alone and in combination over four years in the CombAT study25
Total
Storage
Voiding
Adjusted mean change from
baseline in IPSS
0
-1
-2
‡
*†
-3
-4
*†
-5
-7
Combination therapy
‡
-6
‡
Dutasteride
*†
Tamsulosin
*p<0.001 combination therapy vs dutasteride
†p<0.001 combination therapy vs tamsulosin
‡p<0.001 dutasteride vs tamsulosin
Figure 2. Mean changes from baseline in International Prostate Symptom Score (IPSS; total
score, and storage and voiding subscores) after four years’ treatment with tamsulosin or
dutasteride as monotherapy or combination therapy in the CombAT study27
hip/femur fracture in particular.26 In clinical trials, both were associated with a
small but significant risk of discontinuation due to adverse effects (relative risk:
finasteride 1.08, CI 95% 1.00–1.14;
dutasteride 1.18, CI 95% 1.12–1.24).20
Both drugs were rated “beneficial” for
use in older men with LUTS by the consensus panel. 19 Treatment should be
reviewed after three to six months and
then every 6–12 months.13
The combination of dutasteride with
tamsulosin is more effective than either
agent alone and almost as well tolerated,
improving voiding and storage symptoms
44 ❚ Prescriber January 2017
in men with BPH during long-term treatment (see Figure 2), though not superior
to dutasteride monotherapy in reducing the risk of urinary retention or BPHrelated surgery.25,27
Summary
Many older men with frailty are likely to
have LUTS associated with BPH among
other co-morbidities. Both LUTS and its
treatment can increase the risk of severe
events. Alpha-blockers may increase the
risk of falls and fracture but offer greater
symptom relief than the 5-ARIs, which in
turn are better tolerated and may delay
progression. A careful balance between
benefit and risk is required when considering how best to reduce polypharmacy.
References
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2. Song X, et al. Prevalence and 10-year outcomes of frailty in older adults in relation
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2010;58:681–7.
3. Syddall H, et al. Prevalence and correlates
of frailty among community-dwelling older men
and women: findings from the Hertfordshire
Cohort Study. Age Ageing 2010;39:197–203.
4. British Geriatrics Society. Fit for frailty.
June 2014. www.bgs.org.uk/index.php/
component/content/article/295-resources/
campaigns/fit-for-frailty/2953-fff-guidancedownload
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events among nursing home residents. Arch
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doi: 10.1186/s12916-015-0322-7.
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8. Logie J, et al. Incidence, prevalence and
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BJU Int 2009;104:63-8.
10. NICE. Managing medicines in care homes.
SC1. March 2014. www.nice.org.uk/guidance/
sc1
11. NICE. Multimorbidity: clinical assessment
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www.nice.org.uk/guidance/ng56
12. NICE. Medicines optimisation: the safe and
effective use of medicines to enable the best
possible outcomes. NG5. March 2015. www.
nice.org.uk/guidance/ng5
13. NICE. Lower urinary tract symptoms in
men: management. CG97. May 2010. www.
nice.org.uk/guidance/cg97
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vascular-related safety profile and efficacy
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Clin Pract 2008;62:1547-59.
15. Chrischilles E, et al. Initiation of nonselective alpha1-antagonist therapy and occurrence of hypotension-related adverse events
among men with benign prostatic hyperplasia: a retrospective cohort study. Clin Ther
prescriber.co.uk
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2001;23:727–43.
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hypotension in men aged 40-85 years in the
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Declaration of interests
None to declare.
Steve Chaplin is a medical writer
specialising in therapeutics
Forthcoming events
The forthcoming events section highlights some of the many courses, meetings and
conferences of interest to prescribers planned over the coming months
Nurse Prescribing
Date: 30th January 2017
Venue: De Vere West One, 9-10 Portland Pl, London
Telephone: 01932 429933
Email: www.healthcareconferencesuk.co.uk/contact
Website: www.healthcareconferencesuk.co.uk
This conference will update delegates on their responsibilities
with regard to maintaining nurse prescribing competence for
revalidation and the Nursing and Midwifery Council (NMC) Code.
One Day Essentials | Dermatology
Date: 03 February 2017
Venue: RCGP, 30 Euston Square, London
Telephone: 020 3188 7658
Email: [email protected]
Website: www.rcgpac.org.uk
This One Day Essentials course aims to cover the diagnosis and
management of many of the commonest skin conditions that are
encountered in daily practice, including skin malignancies, psoriasis, dermatitis and red faces.
Nonmedical Prescribing for Pain
Date: 10 February 2017
Venue: De Vere West One, 9-10 Portland Place, London
Telephone: 01932 429933
Email: www.healthcareconferencesuk.co.uk/contact
46 ❚ Prescriber January 2017
Website: www.healthcareconferencesuk.co.uk
This important national conference provides an essential
update for current and aspiring nonmedical prescribers on prescribing for pain.
Advanced Medicine
Date: 13-16 February 2017
Venue: Royal College of Physicians, London
Telephone: 020 3075 2389
Email: [email protected]
Website: www.rcplondon.ac.uk
The Advanced Medicine programme will explore areas of medicine experiencing the most change and innovation, delivered by
eminent speakers in their field.
Mental Health in Primary Care
Date: 22 February 2017
Venue: Rowley Mile Centre, CB8 0TF
Telephone: 01223 884324
Email: [email protected]
Website: www.rcgp.org.uk
This one-day course aims to teach successful techniques that
allow staff in primary care to undertake mental health consultations. The course will raise your confidence in assessing risk
and suicidality and will suggest treatment and support patients
with various mental health problems.
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