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Actions for Practice Teams
Management of primary hypertension
in adults
October 2012
www.pctsla.org
Actions for Practice Teams
Why are we covering this?
•
•
Hypertension is a major preventable cause of morbidity and
mortality
Lowering blood pressure (BP) in patients with hypertension
decreases the risk of1,2:
o
o
o
o
•
2
stroke
coronary events
heart failure
renal impairment
Hypertension may be underdiagnosed in the West Midlands
o QOF-reported prevalence of hypertension in the West Midlands in
2010/11 was 14.6%. Public health (Eastern Region Public Health
Observatory ) estimated prevalence was 32.6%.3
•
Improved identification, diagnosis and treatment of
hypertension could improve outcomes, reduce hospital
admissions and costs to the NHS.
Actions for Practice Teams
What are we covering?
The following slides provide information on primary hypertension in
adults including:
• Background
• Definitions and classification of hypertension
• Risk factors for hypertension and clinical events
• Measurement of blood pressure
• Hypertension diagnosis
• Assessment of cardiovascular (CV) risk and target organ damage
• Lifestyle advice
• Blood pressure targets
• Drug treatment
• Patient education and counselling
• Review of patients with hypertension
We are not covering hypertension in pregnancy or children, secondary
hypertension, accelerated hypertension or acute hypertension in
emergency care settings
3
Actions for Practice Teams
Background
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•
•
•
•
4
Hypertension is defined as a persistently raised BP (above a
designated threshold).
Estimated hypertension prevalence in West Midlands (2011)33.2% of men and 31.0% of women aged over 16 years.3
Hypertension is a major risk factor for stroke, myocardial
infarction, heart failure, chronic kidney disease (CKD),
cognitive decline and premature death.4
Hypertension is usually symptomless- screening and accurate
diagnosis are therefore vital
Diastolic pressure is more commonly elevated in younger
people (age < 50 years). With aging, elevated systolic BP is a
greater problem.4
Actions for Practice Teams
Definitions and classification of
hypertension4
Stage 1 Hypertension
Stage 2 Hypertension
Clinic BP ≥ 140/90
mmHg
AND
Daytime average
ABPM or HBPM ≥
135/85 mmHg
Severe Hypertension
Clinic BP ≥ 160/100
mmHg
AND
Daytime average
ABPM or HBPM ≥
150/95 mmHg
Clinic systolic
BP ≥ 180 mmHg
OR
Clinic diastolic
BP ≥ 110 mmHg
Isolated systolic Hypertension
Systolic BP ≥ 160 mmHg, diastolic BP < 90 mmHg
ABPM = ambulatory BP measurement
HBPM = home BP measurement
5
Actions for Practice Teams
Who is most at risk of hypertension?
Predisposing risk factors for hypertension include5:
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Increasing age
Family history of CV disease
African or Caribbean origin
High intake of salt
Sedentary lifestyle
Co-existing disorders such as diabetes, obesity and
hyperlipidaemia
Smoking
High intake of alcohol
Stress
6
Actions for Practice Teams
Risk factors for clinical events
•
7
The risk of clinical events in hypertensive patients depends on
o BP level
o Calculated CV risk (estimated from factors such as age, gender,
smoking history etc.)
o Presence of target organ damage
o Presence of established CV disease
o Concomitant disease associated with CV risk (e.g. diabetes or
CKD)
•
The risk associated with raised BP is continuous.
o Each 20/10 mmHg rise in BP doubles risk of CV disease across
the entire BP range starting from 115/75 mmHg.6
o Each 2 mmHg rise in systolic BP is associated with increased risk
of mortality (7% from ischaemic heart disease, 10% from stroke).4
Actions for Practice Teams
Measurement of BP
8
Method
Brief Description of equipment
Clinic BP
measurement
An automated device or the auscultatory (listening) method may be
used. The auscultatory method involves use of a sphygmomanometer
(mercury or alternative) and stethoscope by a trained healthcare
professional.
Automated machines detect oscillation in the arterial wall as blood
flows though. Algorithms are used to calculate BP. Easier to use but
less accurate than auscultatory method, particularly if pulse
irregularity.
Home BP
measurement
Fully automated, electronic, oscillometric devices are most commonly
used. Upper arm devices are recommended (wrist and finger devices
discouraged).
BP values tend to be lower than clinic readings and treatment
threshold and targets should be adjusted accordingly.
Ambulatory
BP
measurement
The patient wears a BP cuff attached to an automatic device that
inflates the cuff at regular intervals (e.g. every 20 to 30 minutes during
the day). Readings are recorded by the device and average day or
night BP is determined from the data by a computer. BP readings are
10/5 mmHg lower than clinic BP readings. Ambulatory BP monitoring
monitors use an oscillometric technique and are not suitable for
patients with pulse irregularity.
Actions for Practice Teams
Clinic BP measurement
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9
Detailed information on clinic BP measurement, including an
educational video is available on the British Hypertension
Society (BHS) website (http://www.bhsoc.org/resources/bhsdvd/).
A list of validated BP-measuring devices can be obtained from
the BHS Website (http://www.bhsoc.org/bp-monitors/bpmonitors/) .
Devices for measuring BP should be properly validated,
maintained and regularly recalibrated according to
manufacturer’s instructions
Healthcare professionals taking BP measurements need
adequate training and periodic review of their performance
Actions for Practice Teams
Home BP measurement
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10
A video of home BP measurement and list of suitable devices
are available on the Blood Pressure UK Website
http://www.bpassoc.org.uk/BloodPressureandyou/Thebasics/H
omemonitoring
Advise patients to:
o Choose an upper arm pressure monitor with appropriate
cuff size (finger and wrist monitors are less accurate).
o Always use the same arm. Take three measurements twice
a day in the morning before BP treatment and 12 hours
later.
o Avoid taking measurements when bladder is full, after
exercise or within 30 minutes of taking caffeine or smoking
o Record measurements with date and time, particularly in
relation to when BP tablets are taken.
Actions for Practice Teams
Ambulatory BP monitoring (1)
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Detailed information on ambulatory BP monitoring is now
available on the BHS website. This includes a:
o
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11
Standard operating procedure for ambulatory BP monitoring
Clinic checklist for fitting an ambulatory BP monitor
A patient information leaflet
Patient diary
Ambulatory BP monitoring devices should be validated and
properly maintained. A list of suitable devices is available from
the BHS Website.
Ambulatory BP monitoring machines are sold with software
packages. Some provide basic data (e.g. average day and
night-time values and a visual plot), others provide more detail.
Clinicians responsible for delivering an ambulatory BP
monitoring service should be fully trained.
Actions for Practice Teams
Ambulatory BP monitoring (2)
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12
Patients must be capable of coping with and caring for the
recorder. Consider whether they will be able to cope with the
cuff inflating every half hour.
Relax patient in a quiet room. The ambulatory BP monitoring
process should be explained to the patient.
Consider asking patients to make diary records of events that
are known to affect BP. Sleep times should be recorded.
Instruct patient on how to remove and inactivate monitor after
24 hours.
Actions for Practice Teams
NICE CG127: Hypertension
•
diagnosis4
13
NICE recommend that if the clinic BP ≥ 140/90 mmHg, 24-hour
ambulatory BP monitoring should be offered to confirm the
diagnosis of hypertension.
o Take at least two measurements/hour during the day and use the
average. Use average of at least 14 measurements.
•
Home BP measurement may be used to confirm diagnosis if
ambulatory BP monitoring is unsuitable:
o Two consecutive measurements should be taken at least one
minute apart with the person seated. Use average values (discard
first day’s measurements)
o Record BP twice daily in the morning and evening for ≥ 4 days
(ideally 7 days)
•
If hypertension is not diagnosed, measure BP in clinic at least
every 5 years (more frequently if close to 140/90 mmHg).
o If there is evidence of target organ damage, investigate causes
Actions for Practice Teams
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Why ambulatory BP monitoring for
hypertension diagnosis?
14
Studies suggest that ambulatory BP monitoring is more
accurate than clinic BP measurement for diagnosis of
hypertension.7
“White coat effect” can lead to artificially high clinic BP
readings
Up to 25% of people with high clinic BP readings subsequently
have normal BP on ambulatory BP monitoring4
Ambulatory monitoring is a better predictor of heart disease
and stroke associated with hypertension than single clinic
measurements.8-10
Use of ambulatory BP monitoring for patients with high clinic
BP measurements may reduce misdiagnosis and ultimately
reduce costs.11
Actions for Practice Teams
•
Assessment of CV risk and target
organ damage (1)
15
The 10-year risk of CV disease in hypertensive patients should
be estimated using a validated risk assessment tool. This
should be used to discuss prognosis and healthcare options.4
•
Follow local advice regarding which tool should be used.
•
Examples of validated risk assessment tools are:
o QRISK®2 Cardiovascular Risk Score (http://qrisk.org)
o Joint British Societies risk prediction chart (see BNF or
http://www.bhsoc.org/latest-guidelines/cvd-risk-chart-andcalculators/ )
o Framingham risk equation
(http://hp2010.nhlbihin.net/atpiii/calculator.asp )
Actions for Practice Teams
Assessment of CV risk and target
organ damage (2)
16
The following tests are recommended by NICE to help assess CV
risk, identify diabetes, hypertensive damage to heart and kidney,
and secondary causes of hypertension (e.g. renal disease):
o 12-lead electrocardiogram
o Test urine for presence of protein
o Take blood to measure plasma glucose, electrolytes, creatinine,
estimated glomerular filtration rate, serum total cholesterol and
HDL cholesterol
o Examine fundi for hypertensive retinopathy
•
If initial clinical examination suggests possibility of secondary
hypertension, NICE recommends patient is referred for
specialist review.
Actions for Practice Teams
Specialist referral
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17
If initial clinical examination suggests possibility of secondary
hypertension, NICE recommend patient is referred for
specialist review.4
Refer the same day if
o accelerated hypertension (BP > 180/110 mmHg with signs of
papilloedema and/or retinal haemorrhage)
o suspected phaechromocytoma
Actions for Practice Teams
Key lifestyle advice and associated
BP reductions
Modification
18
Approximate mean BP reduction
Weight reduction
(if overweight)
Cochrane systematic review (2011): mean reduction in
systolic and diastolic BP of 4.5 mmHg and 3.2 mm Hg
respectively12
Exercise
e.g. 30 to 60 mins, 3 to 5
times each week
NICE meta-analysis (2011): mean reduction in systolic
BP (3.1 mmHg) and diastolic BP (1.8 mmHg)4
Alcohol consumption
Men: max 21 unit/week
Women: max 14 unit/week
Meta-analysis of 15 RCTs (2001): mean reduction in
systolic BP of 3.3 mmHg, diastolic BP 2 mmHg13
Dietary sodium reduction
(< 6 g of salt)
NICE meta-analysis (2011): mean systolic BP reduction
of 3.4 mmHg, diastolic BP reduction of 2.2 mmHg4
Caffeine consumption
Consumption of five or more cups a day associated with
small increase in BP14
Smoking cessation
Smoking is associated with poor CV and pulmonary
outcomes
Evidence does not support use of calcium, magnesium or potassium supplementation.4
Relaxation therapies are not provided by the NHS.
Patient information on lifestyle changes is available from the Blood Pressure Association Website
http://www.bpassoc.org.uk/BloodPressureandyou/Yourlifestyle
Actions for Practice Teams
Initiation of drug
treatment4
(1)
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For stage 1 hypertension:
•
If aged less than 80 years, offer antihypertensive drugs to
people if they also have one or more of the following:
o
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target organ damage
established CV disease
renal disease
diabetes
a 10-year CV risk ≥ 20%
If aged 40 to 80 years with none of the above conditions, advise
on lifestyle changes (see slide 18)
If aged ≤ 40 years with none of the above conditions, seek
specialist advice regarding evaluation for secondary causes
If aged > 80 years and newly diagnosed with stage 1
hypertension, decision to treat should be based on the
presence of other co-morbidities
Actions for Practice Teams
Initiation of drug
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treatment4
(2)
All patients with stage 2 hypertension should receive
treatment, regardless of age.
For patients with isolated systolic hypertension, treat as for
patients with both a raised systolic and diastolic BP.
For patients with severe hypertension, consider starting
antihypertensive treatment immediately
20
Actions for Practice Teams
Blood pressure targets
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21
Monitor blood pressure at least annually (more frequently if
titrating drug treatment) using clinic blood pressure
measurements (note: QOF requires practices to record blood
pressure at least every nine months).
In patients with “white coat effect”, consider ambulatory BP
monitoring or home BP measurement as adjunct.
Non-diabetic patients aged less than 80 years4:
o target clinic BP < 140/90 mmHg
o target ambulatory BP or home BP < 135/95 mmHg
Non-diabetic patients aged over 80 years4
o target clinic BP < 150/90 mmHg
o target ambulatory BP or home BP < 145/85 mmHg
Patients with diabetes15
o target clinic BP < 140/80 mmHg (< 130/80 mmHg if kidney, eye or
cerebrovascular disease)
Actions for Practice Teams
Antihypertensive drug treatment
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The choice of a specific drug or a drug combination should
take into account the following:
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NICE/local guidelines
CV risk profile of the patient
Comorbidities
Severity of hypertension
Interactions with drugs used for concomitant conditions
Age
Ethnicity
Previous patient experience of the drug (favourable or
unfavourable)
o Cost
22
Actions for Practice Teams
Antihypertensive therapy:
23
adverse effects/contraindications/monitoring
Contraindications/
Adverse effects
Monitoring
Drug class
Angiotensin
converting enzyme
inhibitors (ACEi)
(e.g. ramipril, lisinopril)
Angiotensin-II
receptor antagonists
(ARBs)
(e.g. losartan, candesartan,
valsartan)
Dihydropyridine
calcium channel
blockers (CCBs)
(e.g. felodipine, amlodipine)
Rate-limiting CCBs
(e.g. diltiazem, verapamil)
Thiazide-like diuretics
(e.g. chlortalidone,
indapamide)
Thiazide diuretics
(e.g. bendroflumethiazide,
hydrochlorthiazide)
precautions
Generally well tolerated
but may cause dry cough
(about 15%), loss of taste,
rarely angioedema, first
dose hypotension,
hyperkalaemia, renal
impairment
Contraindicated in pregnancy,
not recommended if
breastfeeding. Caution in renal
impairment or peripheral
vascular disease.
Monitor renal
function and serum
electrolytes
particularly in
elderly and in renal
impairment.
Well tolerated but may
cause dizziness and
syncope, hyperkalaemia,
impairment of renal
function
Contraindicated in pregnancy,
not recommended if
breastfeeding. Caution in renal
impairment and in peripheral
vascular disease.
Monitor renal
function and serum
electrolytes,
particularly in
elderly and in renal
impairment.
Dihydropyridinesheadache and facial
flushing, tachycardia and
palpitation, ankle swelling
Rate-limiting CCBsbradycardia,
atrioventricular conduction
delay. Verapamil may
cause constipation.
Avoid diltiazem and verapamil
in heart failure. Max dose for
simvastatin in combination with
amlodipine, verapamil or
diltiazem is 20 mg. Do not
combine a beta- blocker with
verapamil, caution with
diltiazem. Prescribe SR
nifedipine and diltiazem
(except 60 mg) by brand.
Hypokalaemia, may cause
or exacerbate diabetes or
gout, hypercalcaemia,
erectile dysfunction
Avoid in gout, not
recommended during
pregnancy. Caution in
combination with beta-blocker.
Monitor renal
function and serum
electrolytes,
particularly
potassium levels.
Actions for Practice Teams
Antihypertensive therapy:
24
contraindications/cautions/monitoring
Drug class
Beta-blockers
(e.g. atenolol,
bisoprolol,
metoprolol)
Alpha blockers
(e.g.doxazosin,
terazosin)
For resistant
hypertension
Adverse effects
Contraindications/
precautions
Bronchospasm in susceptible
individuals, bradycardia, lethargy,
depression, sleep disturbances,
coldness of the extremities, risk of
new onset diabetes, masking of
hypoglycaemia in insulindependent diabetes
Contraindicated in asthma, COPD
with significant reversibility and
heart block.
Caution advised in unstable heart
failure, peripheral vascular disease,
diabetes, with concomitant thiazide
or thiazide-like diuretics. Do not
combine a beta- blocker with
verapamil, caution with diltiazem.
Dizziness, drowsiness, postural
hypotension, headache, flushing,
nasal congestion, fluid retention,
weakness
Vary by drug
Monitoring
Actions for Practice Teams
NICE: Antihypertensive treatmentnon-diabetes4
Based on CG127 Hypertension
slide set, published August 2011
by NICE to be used in conjunction
with guidance CG127
Aged under 55 years
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Aged over 55 years or black
person (African, Caribbean
origin) of any age
CCB
Step 1
ACEi and ARBs
contraindicated Step 2
in pregnancy
Step 3
ACEi or low-cost ARB
(if CCB not suitable, consider thiazidelike diuretic)
ACEi (or low-cost ARB) + CCB (or thiazide-like diuretic if CCB not suitable)
(ARB is preferred to ACEi for black people of African or Caribbean origin)
ACEi (or low-cost ARB) + CCB + thiazide-like diuretic
Resistant Hypertension
Step 4
ACEi (or low-cost ARB) + CCB + thiazide-like diuretic + consider further
diuretic or alpha- or beta-blocker
Consider seeking expert advice
Where possible, use drugs that are taken once a day and prescribe non-proprietary drugs.
Titrate to optimum or maximum tolerated dose at each step of treatment. Unless it is necessary to
lower blood pressure urgently, an interval of at least 4 weeks should be allowed to determine response.
Blood pressure targets:
• If kidney, eye or cerebrovascular damage, set a target < 130/80 mmHg
• Others, set a target < 140/80 mmHg
26
Based on NICE clinical guideline
87 Type 2 Diabetes published in
May 2009
Monitor BP 1-2 monthly until consistently below target
BP above target
Maintain lifestyle measures
Actions for Practice Teams
NICE: Antihypertensive drug treatmenttype 2 diabetes15
Offer ACEi (titrate dose); for people of African-Caribbean
descent, offer ACEi plus diuretic or CCB
BP above target
Add CCB or diuretic
If there is a possibility of
the person becoming
pregnant, start with a CCB.
If continuing intolerance to
ACEi (other than renal
deterioration or
hyperkalaemia), change to
an ARB
BP above target
Add other drug
(diuretic or CCB – see above)
BP above target
Add alpha-blocker, beta-blocker or potassium-sparing
diuretic
Use a potassium-sparing
diuretic with caution if
already taking ACEi or ARB
Actions for Practice Teams
Annual cost comparison of selected
antihypertensive drugs
27
£207.66
irbesartan Aprovel® (75mg to 300mg)
£126.32
£205.57
eprosartan Teveten® (300mg to 800mg)
£95.29
£147.56
felodipine (5mg to 20mg)
£54.88
£129.58
perindopril arginine Coversyl Arginine® (2.5mg to 10mg)
£53.90
£96.73
valsartan capsules (80mg to 320mg)
£37.28
£61.40
candesartan (8mg to 32mg)
£36.50
£50.06
lisinopril (2.5mg to 80mg)
£9.65
£41.37
indapamide M/R (1.5mg)
losartan (25mg to 100mg)
£25.42
£20.21
perindopril erbumine (4mg to 8mg)
£25.29
£23.33
£21.38
chlortalidone Hygroton® (50mg)
ramipril capsules (1.25mg to 10mg)
£15.12
£11.08
indapamide (2.5mg)
£13.56
£11.08
£10.17
amlodipine (5mg to 10mg)
Maximum
£9.26
bendroflumethiazide (2.5mg)
£0
Minimum
£50
£100
£150
£200
£250
Actions for Practice Teams
Other measures to reduce CV risk
•
Review use of drugs that may potentially exacerbate
hypertension (prescribed or OTC) including:
o
o
o
o
o
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28
Non-steroidal anti-inflammatory drugs (NSAIDs)
Soluble analgesics (high sodium content)
Combined hormonal contraceptives
Steroids
Sympathomimetics (in some cold medicines)
Additional therapy to lower CV risk should be considered for
patients with target organ damage, established CV disease,
diabetes, CKD or estimated 10 year CVD risk ≥ 20%
o Aspirin for patients with established CV disease (unless
contraindicated)
o Aspirin is not licensed for primary prevention of vascular events
and is of unproven benefit (with or without diabetes).16-20 Consider
benefits and risks for each individual.
o Statins should be used in line with NICE guidance on lipid
lowering drugs (CG67). 21
Actions for Practice Teams
Patient education and counselling (1)
•
•
•
Repeated in-depth patient education and counselling improves
adherence to treatment and reduces CV risk factors.
Support adherence to antihypertensive drugs as this is often
suboptimal. Poor adherence has been associated with complications
including CV death.
o Recent systematic review suggests that adherence may be
particularly poor in those prescribed diuretics and beta-blockers22
Interventions to support adherence may include23:
o
o
o
o
o
•
29
suggesting that patients record their medicine-taking
encouraging patients to monitor their condition
simplifying the dosing regimen
using alternative packaging for the medicine
using a multi-compartment medicines system.
Explain that although high BP is usually symptomless, it increases the
chance of strokes, heart attacks, heart failure, or kidney failure.
Actions for Practice Teams
Patient education and counselling (2)
•
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Provide information on benefits and side effects of drugs.
o Advise patients on what to do if they develop an adverse reaction
to their medication
o Explain that hypertensive medication usually needs to be taken
for life.
•
Advise patients that although medication may be stopped if
blood pressure becomes well controlled, particularly after
lifestyle changes, it should be regularly checked thereafter
o Blood pressure may rise again a year or more after treatment
withdrawal
•
•
Discuss appropriate lifestyle changes (see slide 18)
Patient information on blood pressure and antihypertensive drugs is
available from Blood Pressure UK (http://www.bpassoc.org.uk ) and
the British Heart Foundation (http://www.bhf.org.uk )
Actions for Practice Teams
Follow-up and monitoring
•
•
•
•
•
31
NICE recommend that patients with hypertension are reviewed
annually
Check blood pressure, renal function and test for proteinuria
Reinforce lifestyle advice and check adherence to
antihypertensive drugs
Is a change to antihypertensive drug treatment indicated?
Consider:
o Is blood pressure adequately controlled?
o Adverse effects?
If the person is not taking a statin, assess CV risk and consider
whether this treatment would be appropriate. For patients
requiring secondary prevention, review need for antiplatelets.
Actions for Practice Teams
References
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24)
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Lv J, Neal B, Ehteshami P et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: a systematic review and meta-analysis. PLoS Med
2012;9:e1001293.
East of England Public Health Observatory. Modelled estimate of prevalence of hypertension in England. 2011 http://www.apho.org.uk/resource/item.aspx?RID=111119
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Chobanian AV, Bakris GL, Black HR et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
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Hodgkinson J, Mant J, Martin U et al. Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in
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Ohkubo T, Hozawa A, Nagai K et al. Prediction of stroke by ambulatory blood pressure monitoring versus screening blood pressure measurements in a general
population: the Ohasama study. J Hypertens 2000;18:847-54.
Staessen JA, Thijs L, Fagard R et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic
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Xin X, He J, Frontini MG et al. Effects of Alcohol Reduction on Blood Pressure. Hypertension 2001;38:1112-7.
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Baigent C, Blackwell L, Collins R et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from
randomised trials. Lancet 2009;373:1849-60.
Fowkes FG, Price JF, Stewart MC et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized
controlled trial. JAMA 2010;303:841-8.
De Berardis G, Sacco M, Strippoli GF et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials.
BMJ 2009;339:b4531.
Lip GYH, Felmeden DC, Dwivedi G. Antiplatelet agents and anticoagulants for hypertension. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No.:
CD003186. DOI: 10.1002/14651858.CD003186.pub3
Aspirin: not licensed for primary prevention of thrombotic vascular disease. Drug Safety Update. Volume 3, Issue 3. Medicines and Healthcare products Regulatory
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Lipid modification. CG67. National Institute for Health and Clinical Excellence. 2008. http://www.nice.org.uk/nicemedia/live/11982/40689/40689.pdf <accessed 9/2012>
Kronish IM, Woodward M, Sergie Z et al. Meta-analysis: impact of drug class on adherence to antihypertensives. Circulation 2011;123:1611-21.
Medicines adherence: Involving patients in decisions about prescribed medicines and supporting adherence. CG76. National Institute for Health and Clinical Excellence.
2009. http://publications.nice.org.uk/medicines-adherence-cg76/guidance#supporting-adherence <accessed 7/2012>
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