School of Pharmacy & Life Sciences Version: 2024.

Hypertension

Topic Overview

This topic focuses on the management of essential hypertension.

Learning Objectives

On completion of this topic, you should be able to:

• demonstrate comprehensive, detailed understanding of the pathophysiology of hypertension

• demonstrate up-to-date knowledge of the therapeutics of and evidence-based guidelines for
the management of essential hypertension
• compare and contrast pharmacological agents used in the management of hypertension
• discuss current issues in the management of hypertension including the concept of
cardiovascular risk
• critically evaluate therapeutic regimens used in the management of hypertension in individual
patients
• formulate advice for patients and healthcare professionals relating to the management of
hypertension.

Background

The definition of hypertension is arbitrary and varies in different countries. There is no natural cut-off
point above which ‘hypertension’ definitely exists and below which it does not. In the UK, hypertension
is suspected if a clinic blood pressure is >140mmHg (systolic) and/or > 90mmHg (diastolic). The diagnosis
is then confirmed with ambulatory blood pressure monitoring (ABPM) or home blood pressure
monitoring (HBPM) (NICE 2019, Ng and Lobo 2018). The most recent American College of Cardiology /
American Heart Association (ACC/AHA) (2017) guidelines have lowered the BP threshold for diagnosis
and treatment targets. NICE guidance for the UK was published in August 2019 and retains the previous
definition of hypertension, as do the latest European guidelines. A scientific statement released by AHA
in 2021 offers new guidance on blood pressure management of Stage 1 Hypertension among patients
with low cardiovascular disease risk (Jones et al, 2021). NICE guidance was updated in 2022 with new
recommendations to cover people who have both hypertension and cardiovascular disease.

Around 90-95% of patients with hypertension have primary or essential hypertension where there is no
single identifiable cause; rather it will be the result of a complex interaction of environmental and genetic
factors. The remaining small proportion of hypertensive patients have secondary hypertension where
the condition has an identifiable and often remediable cause. Common causes of secondary
hypertension are endocrine in nature (phaeochromocytoma, Conn’s Syndrome), vascular (renal artery
stenosis), renal disease or may be drug-induced (Ng and Lobo 2018).

It is well established that blood pressure rises with age in all individuals thus the prevalence of
hypertension also increases with age. Hypertension affects at least a quarter of the adult population and
more than half of those older than 60 years (NICE 2019). It is the most common reason for consulting a
doctor in general practice in men aged 45 years and above and in women aged over 65 years in the UK.
Prevalence is increasing secondary to levels of obesity in the population. The 2019 NICE guidance made
new recommendations on diagnosis, monitoring and drug treatment of hypertension, and on identifying
whom to refer for same-day specialist review.

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Identification and Management

The identification and management of hypertension is an important public health issue as hypertension
is a major reversible risk factor for cardiovascular disease and other pathologies. Complications of
hypertension include ischaemic and haemorrhagic stroke, myocardial infarction, heart failure, chronic
kidney disease and retinopathy. Hypertension should not be treated in isolation and other
cardiovascular risk factors should be addressed concurrently (NICE 2019).

Primary hypertension is predominantly an asymptomatic condition, often detected in a primary care

setting – either as a result of routine screening in general practice or community pharmacy or more
commonly as an incidental finding. Many patients unfortunately will only have hypertension diagnosed
after they have suffered a cardiovascular event.

Diagnosis

A diagnosis of hypertension will commit the majority of patients to lifelong treatment and monitoring,
and it is therefore important to ensure that an accurate diagnosis is made. It is recommended that
immediate referral for specialist assessment carried out on the same day is made in patients who present
with a blood pressure of 180/120mmHg and higher with signs of papilloedema or retinal haemorrhage
(accelerated hypertension) or life-threatening symptoms such as new onset confusion, chest pain, signs
of heart failure or acute kidney injury for further investigation and to allow management of secondary
causes of hypertension if subsequently diagnosed. Patients with suspected phaeochromocytoma should
also be similarly referred and may present with labile or postural hypotension, headache, palpitations,
pallor and diaphoresis. (NICE 2019).

In most patients, however, treatment should not be commenced based on a single raised blood pressure
measurement. Previous guidance recommended that there should be a period of follow-up, during which
time the patient could be fully assessed, lifestyle changes implemented and blood pressure monitored
regularly. The latest advice recommends offering ambulatory blood pressure monitoring (ABPM) to
confirm the diagnosis of hypertension if the clinic BP is between 140/90mmHg and 180/120mmHg. If a
person is unable to tolerate ABPM, home blood pressure monitoring (HBPM) is recommended.
Consideration should be given to starting antihypertensive drug treatment immediately if the clinic BP is
>180/120mmHg and target organ damage is identified. If no target organ damage is identified, clinic BP
should be repeated within 7 days (NICE 2019).

While waiting for confirmation of diagnosis, investigations for target organ damage (such as left
ventricular hypertrophy, chronic kidney disease and hypertensive retinopathy) should be carried out and
an assessment of cardiovascular risk made using a cardiovascular risk assessment tool (NICE 2019).

The management of patients (other than those with secondary, malignant or resistant hypertension) will
be within the primary care environment and will be the responsibility of a multidisciplinary team of
general practitioners, nurses and pharmacists

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Click on the picture to

listen to the most up to
date BMJ Best Practice
Hypertension podcast
from BMJ Talk Medicine.

Treatment

The main treatment goal for hypertension is to reduce the incidence of cardiovascular complications.
The management of a patient with hypertension should therefore be aimed at not only lowering blood
pressure but also aimed at lowering their absolute risk of cardiovascular disease. To maximise the
lowering of morbidity and mortality, the treatment of patients with hypertension may necessitate the
use of cholesterol-lowering drug therapy following assessment of cardiovascular risk, in addition to
lowering other risk factors (e.g., smoking cessation). Patients with type 2 diabetes mellitus are at
significant risk of cardiovascular events, similar to those with established cardiovascular disease (e.g.,
patients with stroke or coronary heart disease). Recent guidelines suggest blood pressure lowering
treatment for individuals with type 2 diabetes if the baseline clinic systolic pressure is >140mmHg to
prevent mortality, macrovascular events and progression of nephropathy and retinopathy (SIGN 2017).
Treatment should be considered even if the systolic clinic blood pressure is <140mmHg in patients with
diabetes thought to be at greatest risk of complications, to reduce the risk of stroke, progression of
retinopathy and albuminuria.

Evidence for the benefits of aspirin in primary prevention is weak. Previously, it was advised that the use
of aspirin for primary prevention should be based on individual risk assessment, considering both
cardiovascular risk and risk of gastrointestinal bleeding (MHRA 2009). However, the 2017 SIGN guideline
does not recommend aspirin for the primary prevention of cardiovascular disease in patients with
hypertension (SIGN 2017). This is in agreement with guidance from the Joint British Societies for the
prevention of cardiovascular disease (JBS 2014).

The following British Heart Foundation video on ‘High blood pressure and heart disease’ describes one
patient’s experiences and motivation in making changes to reduce her risk of developing heart disease.
click on the picture to view

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Although non-pharmacological approaches, such as weight reduction if overweight/obese, regular

exercise, minimisation of salt intake and reduction of alcohol intake, are integral to the management of
hypertension, the use of drugs is central to the treatment of this condition. There are many classes of
antihypertensives available (thiazide-like diuretics, ACE inhibitors, Angiotensin-II receptor antagonists,
calcium channel blockers, beta-blockers and others), all of which will effectively lower blood pressure.
Most drugs and drug classes have outcome data from long-term randomised controlled trials that
demonstrate reductions in cardiovascular morbidity and mortality (NICE 2019).

The publication of the ALLHAT (Anti-hypertensive and Lipid-Lowering treatment to prevent Heart Attack)
trial, the largest published outcome trial for antihypertensives, confirmed the importance of lowering
blood pressure by use of drugs. Participants were randomised to receive a thiazide-like diuretic, a calcium
channel blocker, or an ACE inhibitor. There was no significant difference between groups in reducing
cardiovascular events (ALLHAT 2002). The ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial –
Blood Pressure Lowering Arm) study found that antihypertensive therapy based on amlodipine with
perindopril added as required, was significantly more effective at reducing strokes, cardiovascular events
and all-cause mortality compared with treatment based on atenolol with bendroflumethiazide added if
required (Dahlöf et al. 2005).

New evidence in key areas resulted in the publication of updated British Hypertension Society (BHS)
guidelines in 2004. These guidelines recommended the use of the AB/CD treatment algorithm for initial
therapy in the absence of a compelling indication for one of the major classes of antihypertensive drugs.
Following a review of outcomes of clinical trials involving the use of beta-blockers in hypertension, NICE
and the BHS produced a joint updated guideline published in 2006 which revised the AB/CD algorithm to
A/CD. This removed the previously established recommendation that beta-blockers are prescribed in the
routine management of hypertension. This reflected evidence that the combination of beta-blockers and
thiazide diuretics in some hypertensive patients with risk factors for diabetes mellitus (such as obesity)
may increase the incidence of type 2 diabetes. Furthermore, it took account of evidence suggesting beta-
blockers were less likely to decrease the incidence of stroke and myocardial infarction in hypertensive
patients when compared with other antihypertensive agents. A further updated guideline in
hypertension management commissioned by NICE was published in 2011 and updated in 2019, with
minor additions in 2022. Thiazide diuretics are no longer recommended as first-line treatment unless
other indications exist, with calcium channel blockers now being preferred first drugs for people over 55
years of age and people of black African or African-Caribbean family origin. Although
bendroflumethiazide is widely used in the UK, it is less commonly prescribed elsewhere and evidence is
absent for use at the doses prescribed in current UK practice. Indapamide is suggested as an alternative
(NICE 2019).
Previously, there was uncertainty about the benefits and risks associated with the treatment of very
elderly people with hypertension. However, the HYVET (Hypertension in the Very Elderly) trial showed
that the use of antihypertensive drugs to reduce blood pressure in patients aged 80 years or more was
associated with a significant and marked reduction in the incidence of stroke and heart failure. It also
found that treatment reduces all-cause mortality. A follow-up study showed that treating people over
80 had sustained benefits and that earlier treatment resulted in lower mortality (Beckett 2012). This
supported the need for early and long-term treatment of hypertension in elderly patients.

The selection of one antihypertensive as initial treatment for an individual patient will depend upon an
assessment of that patient to establish their concomitant pathologies, which may compel the use of a
particular drug class, as well as the presence of any factors that contraindicate the use of a particular
drug class. Additionally, achieving concordance between the patient and healthcare professionals
treating hypertension is important in this asymptomatic patient population to ensure compliance with
treatment, as is ongoing patient education. Increasingly, some patients are taking responsibility for
ongoing monitoring of their hypertension through measurement of blood pressure in the home

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environment, however, it is important to ensure the accuracy of the automated meters used and the
validity of the readings taken. Self-monitoring has been shown to improve control of high blood pressure
compared with GP monitoring alone and could benefit patients by preventing stroke and heart disease
(McManus et al 2018). Evidence on the role of home blood pressure monitoring (HBPM) is evolving.
Education, ongoing support and engagement with patients appear to be important to its success. HBPM
is superior to clinic blood pressure measurements in predicting future cardiovascular events (Khong and
Fok 2021).

It should be recognised that most patients would require treatment with more than one antihypertensive
agent to reach the desired target levels. The use of combinations of two or more antihypertensives
increases the potential for adverse reactions and may affect compliance. Currently, it is recommended
that, before considering the next step in treatment for hypertension, it should be discussed with the
person if they are taking the medicine as prescribed (discuss adherence). The person’s medications
should be reviewed to ensure that they are being taken at the optimal tolerated doses. There is little
evidence to date of benefit for particular combinations of antihypertensives, but models such as the A/CD
algorithm, as recommended by NICE /BHS in 2006 and updated in 2011 and 2019, do offer some
guidance in selecting appropriate add-on therapy.

It has been suggested that evening dosing with antihypertensive therapy might allow better blood
pressure control than morning dosing. However, a recent study showed that evening dosing of usual
antihypertensive medication was not different from morning dosing in terms of major cardiovascular
outcomes. Patients can therefore be advised to take their medication at a time that suits them best
(Mackenzie IS et al 2022).

The Joint British Societies (JBS) risk calculation tables contained within the BHS guideline were previously
the recommended means of assessing 10-year cardiovascular risk for patients with hypertension in the
UK. The tables are based on the results of the Framingham study, conducted in the 1960s in middle-
class America. NICE withdrew the recommendation that the Framingham risk equation should be the
equation of choice for the assessment of CVD risk in 2010 but agreed that it should be considered as one
of the possible equations to use. Evidence has shown that the use of the Framingham data to calculate
risk in populations today may underestimate cardiovascular risk in certain sections of the population,
e.g., British Asians. The latest recommendation from NICE is to use the QRISK2 risk assessment tool to
assess cardiovascular disease risk for the primary prevention of cardiovascular disease in people up to
and including 84 years (NICE 2014). The QRISK2 calculator more accurately assesses risk in the UK
population, is available online (www.qrisk.org) and is updated annually (HIPPISLEY-COX, J., 2018).
QRISK3 was published in 2017 and includes more factors to identify those at the most risk of heart
disease and stroke. There is also evidence that social deprivation and family history of premature
cardiovascular disease are key additional factors influencing the risk of a cardiovascular event within the
Scottish population and the ASSIGN risk calculator within the current SIGN guideline encompasses this.
The ASSIGN risk calculator is used to assess cardiovascular risk in Scotland (ASSIGN 2014, SIGN 2017).
The Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease
(JBS3) risk score, based on the QRISK2 algorithm developed for use in England and Wales, also now
includes a measure of social class as well as family history of premature cardiovascular disease (JBS3
2014).

A quality standard for hypertension was published by NICE in 2013 and updated in 2015 (NICE QS28).
This describes measurable markers of high-quality, cost-effective care to drive improvement in the
effectiveness, safety and experience of care for people with hypertension.

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Pharmacists working in a hospital, general practice and community pharmacy may all be involved in the
care of patients with hypertension, through prescribing, monitoring, or advising on lifestyle modification
and supporting changes.

The following video from the British Heart Foundation describes how one community pharmacist
supports patients with hypertension with lifestyle and behaviour changes to help reduce blood pressure.

Click on
the
picture to
view

References

The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, 2002. Major
outcomes in high-risk hypertensive patients randomised to Angiotensin Converting Enzyme Inhibitor or
Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering treatment to prevent
Heart Attack Trial (ALLHAT). Journal of the American Medical Association, 288(23): pp.2981-2997.

ASSIGN, 2014. Estimate the risk using the ASSIGN Score. [online] Dundee: Cardiovascular Epidemiology
Unit, University of Dundee. Available from: http://assign-score.com [Accessed 31 October 2023]

BECKETT, N.S. et al., 2008 (for the HYVET study group). Treatment of hypertension in patients 80 years
of age or older. New England Journal of Medicine, 358: pp.1887-1898.

BECKETT, N.S. et al., 2012. Immediate and late benefits of treating very elderly people with
hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised
controlled trial. British Medical Journal, 344:d7541.

DAHLÖF, B. et al., 2005. Prevention of cardiovascular events with an antihypertensive regimen of

amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in
the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a
multicentre randomised controlled trial. Lancet, 366 (9489): pp.895-906.

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HIPPISLEY-COX, J., 2018. QRISK3 cardiovascular disease risk calculator. [online]. Nottingham: University of
Nottingham. Available from: http://qrisk.org [Accessed 31 October 2023]

JBS3 Board, 2014. Joint British Societies’ consensus recommendations for the prevention of
cardiovascular disease (JBS3). Heart, 100 Suppl 2: pp.ii1-ii67.

JONES, D.W. et al., 2021. Management of Stage 1 Hypertension in adults with a low 10-year risk for
cardiovascular disease: Filling a guidance gap: A scientific statement from the American Heart
Association. Hypertension, 77: e58-e67.

KHONG, T.K. and FOK, H., 2021. Home blood pressure monitoring: What does the evidence say? Drug
and Therapeutics Bulletin, 59: pp.119-123.

MACKENZIE, I.S. et al., 2022. Cardiovascular outcomes in adults with hypertension with evening versus
morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-
label, blinded-end point clinical trial. The Lancet 400 (10361) 1417–1425.

McMANUS, R.J. et al., 2018. Efficacy of self-monitored blood pressure, with or without telemonitoring,
for titration of antihypertensive medication (TASMINH4); an unmasked randomised controlled trial. The
Lancet 391 (10124) 949-959.

MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY, 2009. Drug Safety Update Volume 3
Issue 3. [online]. London: Medicine and HealthCare Products Regulatory Agency. Available from:
http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/index.htm. [Accessed 31 October
2023].

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE, 2019 (updated 2022). Hypertension in adults:
diagnosis and management. [online]. London: National Institute for Health and Clinical Excellence.
Available from: https://www.nice.org.uk/guidance/ng136 [Accessed 31 October 2023]

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE 2014. Cardiovascular disease: risk
assessment and reduction, including lipid modification. [online] London: National Institute for Health
and Clinical Excellence. Available from: http://guidance.nice.org.uk/CG181 [Accessed 31 October
2023]

NG, F. L. and LOBO, M. D., 2018. Investigation and management of adult hypertension. Heart 104:1543-
1551 https://heart.bmj.com/content/104/18/1543 [Accessed 31 October 2023]

SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK (SIGN), 2017. Risk estimation and the prevention of
cardiovascular disease. [online]. Edinburgh: Scottish Intercollegiate Guidelines Network. Available
from:
https://www.sign.ac.uk/sign-149-risk-estimation-and-the-prevention-of-cardiovascular-disease
[Accessed 31 October 2023]

WHELTON, P.K. et al., 2018. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/ NMA/PCNA

guideline for the prevention, detection, evaluation, and management of high blood pressure in adults:
Executive Summary: a report of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines.
Hypertension 71(6):1269-1324 https://www.ahajournals.org/doi/10.1161/HYP.0000000000000065
[Accessed 31 October 2023]

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Web Resources

BRITISH AND IRISH HYPERTENSION SOCIETY website

• This website provides links to up-to-date guidelines for the management of hypertension and
relevant fact files.
• A fact file ‘Statement on the use of Aspirin’ with additional references is available for further
reading on aspirin for primary prevention of cardiovascular disease.

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE, 2019 (updated 2022). Hypertension in adults:
diagnosis and management. [online]. London: National Institute for Health and Clinical Excellence.
Available from:
https://www.nice.org.uk/guidance/ng136 [Accessed 31 October 2023]

• See also NICE pathways (Hypertension) - hypertension pathway, a fast, easy summary view of
NICE guidance on 'hypertension'

WILLIAMS, B. et al., 2018. 2018 ESC/ESH Guidelines for the management of arterial hypertension.
European Heart Journal 39 (33): 3021-3104.
https://doi.org/10.1093/eurheartj/ehy339 [Accessed 31 October 2023]
• Updated European Society of Cardiology and European Society of Hypertension guidelines

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