According to the National Institute for Health and Care Excellence (NICE, 2019a), the definition of hypertension is ‘persistently raised arterial blood pressure’. However, use of the term ‘raised’ is open to interpretation, as the range of normal blood pressure (BP) readings in the general population is widely distributed, and comorbidities such as chronic kidney disease can affect recommended targets (NICE, 2021).
In its guideline on hypertension diagnosis and management, NICE states that exceeding an upper limit of 140 mmHg systolic BP and/or 90 mmHg diastolic BP is when a diagnosis of hypertension should be suspected. Home blood pressure monitoring is recommended as the preferred method of confirming the diagnosis. Wherever the BP is measured, and whoever is doing it, correct technique should be used and repeated measurements taken to confirm the accuracy of the readings (Nitzan et al, 2017).
Primary (essential) hypertension refers to the presence of high blood pressure that is most likely the result of ageing or lifestyle factors such as obesity and that is not linked to other underlying disease, such as renal disease, endocrine disorders or genetic conditions. Around 95% of all cases of hypertension are essential hypertension, meaning that 5% of cases are so-called secondary hypertension (Iqbal and Jamal, 2023). Secondary hypertension may be suspected in younger people (under 40 years of age) or in cases of resistant hypertension, where three drug classes have failed to get the BP to target (NICE, 2019a). In these cases, referral to specialist care for further investigations should be made (NICE, 2019a).
Home BP readings are important to get a better idea of whether BP is controlled away from the clinical setting, where ‘white coat hypertension’ may occur. This is defined by NICE as present when there is a discrepancy of more than 20/10 mmHg between clinic and average home BP readings at the time of diagnosis. Importantly, the presence of white coat hypertension is associated with an increased risk for both cardiovascular events and all-cause mortality, so should not be missed (Cohen et al, 2019).
Postural hypotension refers to a sustained reduction in systolic blood pressure of at least 20 mmHg, or a reduction in diastolic blood pressure of at least 10 mmHg, when moving from lying or sitting to standing (NICE, 2019a). Postural hypotension may increase the risk of symptoms, such as dizziness and falls, so NICE recommends that elderly people, those with diabetes and anyone with symptoms of postural hypotension, should have sitting and standing blood pressure measurements taken to identify postural hypotension. If this is diagnosed, the lower reading should be used to inform management, which may involve deprescribing of medication (NICE, 2019).
Masked hypertension is said to be present when the clinic BP is normal (less than 140/90 mmHg) but home BP readings are elevated. Up to 10% of the population may suffer from masked hypertension, which, if undiagnosed, can increase the risk of target organ damage and cardiovascular events to levels close to those of standard hypertension (Cuspidi et al, 2019). The increased use of home BP monitoring may help to identify white coat hypertension, postural hypotension and masked hypertension.
Recommended targets
NICE (2019a) recommends a clinic BP target of below 140/90 mmHg or a home BP target of 135/85 mmHg. In people over the age of 80 years, a higher cut-off point of 150/90 mmHg in clinic, or 145/85 mmHg at home is advised. Evidence suggests that this higher target should be used in older people because the risk:benefit ratio of treatment will be affected by age, frailty and co-morbidities and these elements may increase the risk of falls and fractures (NICE, 2016).
Ruths et al (2015) carried out a cohort study in Norway to see whether specific classes of antihypertensives were associated with an increased risk of falls and hip fractures. The study found that, although there was a reduced risk of hip fracture associated with overall use of most antihypertensive drugs, including in the over-80s, there was an increased risk of hip fracture with loop diuretics and ACE inhibitors among people younger than 80 years and in new users of loop diuretics.
Although the risk of postural hypotension has been noted, it is still important to diagnose and treat hypertension in older people. The Hypertension in the Very Elderly Trial (HYVET) studied 3845 people aged 80 and above, and demonstrated reductions in cardiovascular events, particularly fatal stroke and heart failure when hypertension was diagnosed and treated (Beckett et al, 2008). A target of 150/80 mmHg achieved improved outcomes without increasing risk.
The Systolic Blood Pressure Intervention Trial (SPRINT) included 2636 patients over the age of 75 years who measured their own BP in a doctor's surgery. The results showed that achieving lower BP targets (the mean achieved in the active group was 124/62 mmHg) reduced the risk of major cardiovascular events, heart failure and all-cause mortality, compared with the comparator group's target BP of 135/67 mmHg (Wright et al, 2015). When guidelines from the US recommended tighter targets in older people, Nayor et al (2018) showed that people aged 60 and above with a BP between 140 and 149 mmHg, and a diastolic BP of 90 mmHg or lower (with or without treatment), had a consistently higher incidence of cardiovascular events. Overall, clinicians should consider the age of the individual being treated, along with comorbidities, frailty and biological age to determine the most appropriate target.
‘Clinicians who prescribe medication for hypertension should be familiar with the mode of action, indications and side effects of the range of drugs recommended’
The NICE (2019a) hypertension guidelines recommend pharmacological interventions for stage one hypertension (135/85–149/94 mmHg) with a cardiovascular risk score of 10% or more, and/or in those with target organ damage or diabetes. In stage 2 hypertension (BP 150/95 mmHg or higher), pharmacological management is always recommended. The aim is to reduce BP to below 140/90 mmHg (clinic readings) or below 135/85 mmHg based on home readings.
The European Society of Hypertension (ESH, 2023) guidelines go further than this, recommending a target BP of <130/80 mmHg for those aged 18–64, <140/80 mmHg in the 65–79 age group and 140–150/<80 mmHg in those age 80 and over. In the over-80s who are not frail, a target of <130/80 mmHg may be considered with caution. However, the ESH recommendations state that treatment of hypertension should not result in a BP of <120/70 mmHg unless a lower systolic reading can only be achieved by further reducing the diastolic BP.
Pharmacological treatment
The Royal Pharmaceutical Society (RPS) has produced a competency document, which supports a holistic approach and informs good practice in prescribing (RPS, 2021). Clinicians who prescribe medication for hypertension should be familiar with the mode of action, indications and side effects of the range of drugs recommended to treat hypertension. Resources such as those available from the Electronic Medicines Compendium (https://www.medicines.org.uk/emc) include information on therapeutic indications, side effects, interactions, cautions and contraindications. Patient information is available from the British Heart Foundation's Drug Cabinet section, which can be found here: https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/drug-cabinet.
NICE guidance (2019a) recommends that people under the age of 55, or those with diabetes, should be prescribed an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) first-line, with the addition of a calcium channel blocker (CCB), such as amlodipine and/or a thiazide diuretic (for example, indapamide), as needed. In those aged 55 and above, or those of black African or African–Caribbean ethnicity, a CCB should be started first-line with an ACEi and/or a thiazide-like diuretic added in, where indicated, to get to target. Drugs may be uptitrated before other medication is added in, although smaller doses of two drugs is more likely to get people to target than higher doses of one drug. However, the presence of co-morbidities such as cardiovascular disease, heart failure or diabetes would mean that ACE inhibitors should be titrated to the maximum tolerated dose in order to optimise cardiorenal protection (Neal et al, 2000; Xie et al, 2015).
‘Discussions should be open and inclusive, with the patient being encouraged to ask their own questions so that the clinician can tailor advice and support to the needs and wishes of each individual’
All medication recommendations should be discussed with the patient, explaining the reason it is being recommended, the mode of action, key potential side effects, other options that may be available and the option to decline medication (RPS, 2021). Discussions should be open and inclusive, with the patient being encouraged to ask their own questions so that the clinician can tailor advice and support to the needs and wishes of each individual, in line with the Montgomery ruling on informed consent (Medical Defence Union, 2023).
Medication classes
ACEis and ARBs have an impact on the renin angiotensin aldosterone system (RAAS). ACEis reduce the conversion of angiotensin I to angiotensin II, a potent vasodilator that also facilitates water and salt retention. The effect of ACE inhibition, then, is to reduce vasoconstriction, fluid and salt retention, which in turn reduces blood pressure (Goyal et al, 2023). ARBs affect the RAAS by blocking the effect of angiotensin II, rather than interrupting the conversion of angiotensin I to angiotensin II. ARBs have less impact on bradykinin levels, and therefore reduce the risk of bradykinin-mediated ACE-induced cough (Hill and Vaidya, 2023). RAAS inhibition with ACEi and ARBs has a positive impact on blood pressure, the kidneys and the cardiovascular system in general.
Prescribing of ACEi and ARBs should start with low doses, which are then gradually uptitrated. As an example, after assessing renal function, ramipril 2.5 mg can be initiated, with renal function and BP being checked after 10–14 days. Assuming changes in renal function are less than 25% in eGFR or 50% in creatinine, the dose can be increased to 5 mg and after reassessing renal function and BP to the optimal dose of 10 mg, if tolerated. A useful tool on addressing the impact of RAASi drugs on renal function can be found here: https://www.theisn.org/initiatives/toolkits/raasi-toolkit.
The change in BP between 5 mg and 10 mg is small but the cardiorenal benefits of optimisation are significant. In a recent meta-analysis, one in 33 patients on ACE inhibitors developed hypotension (Na et al, 2022). If further BP control is needed, additional therapy should be introduced. Although maximum tolerated doses of RAASi drugs have the most benefit on cardiorenal outcomes, smaller doses of different drug classes are likely to optimise BP control while reducing the risk of side effects. It is important to consider the aim of treatment for each individual, engage in a shared decision-making approach with the patient, and prescribe accordingly.
Side effects of ACE inhibitors include cough, and doses may need to be restricted in people with renal impairment. If ACE-induced cough occurs, an ARB should be substituted as these drugs work by blocking the effect of angiotensin II rather than affecting the conversion of angiotensin I to angiotensin II, which is where the bradykinin-mediated side effect of cough occurs.
Calcium channel blockers act primarily as vasodilators. NICE (2019a) states that they are first-line for people aged 55 and above as the vasodilatory action is more likely to reduce BP effectively in this age group. NICE also recommends CCBs for people of African–Caribbean ethnicity, although ARBs may be preferred in people in these ethnic groups who also have diabetes (NICE, 2019a). There are two types of CCBs: dihydropyridines (such as amlodipine and lercanidipine), which are used for BP management; and the non-dihydropyridines (such as diltiazem and verapamil), which are useful as anti-arrythmia drugs (McKeever and Hamilton, 2022). CCBs can be used at the dose that enables optimal BP control e.g., amlodipine 5–10 mg.
BP monitoring is the key requirement for CCB therapy, as hypotension may occur. Common side effects of CCBs include ankle oedema, flushing, headaches and constipation.
Thiazide-like diuretics promote natriuresis and diuresis to lower BP and include indapamide and chlortalidone (Akbari and Khorasani-Zadeh, 2023). Unlike loop diuretics, thiazide-like diuretics do not have a potent diuretic effect, but they do have a vasodilatory effect, which will bring about a reduction in blood pressure. They are usually prescribed at a fixed dose, e.g. indapamide 2.5 mg daily. Renal function should be monitored for anyone taking a diuretic along with assessment of blood pressure control and assessing for side effects, which include electrolyte imbalances.
‘Hyperkalaemia is one of the key potential side effects of spironolactone and is linked with the risk of acute kidney injury, particularly in patients on aspirin or other non-steroidal anti-inflammatory drugs’
Most people will achieve recommended BP targets on two or three medication types and NICE guidelines for prescribing in hypertension reflect this (NICE, 2019a). Failure to achieve targets on three drug classes means that non-adherence and confounding factors should be identified and addressed. Lifestyle factors, including high salt or alcohol intake, may be linked to both the diagnosis of hypertension and the reduced effect of antihypertensive medication (Yaxley and Thambar, 2015). As a result, interventions such as reducing salt and alcohol intake, weight management and smoking cessation should all be recommended at diagnosis and before adding medication.
If, despite all of this, blood pressure targets have not been achieved and the individual is being treated with three classes of antihypertensive drugs at maximally tolerated doses, the diagnosis of resistant hypertension (RH) would apply (NICE, 2019a; ESH, 2023). However, non-adherence may be the underlying cause of RH as up to 50% of people diagnosed with and treated for hypertension have suboptimal adherence (Burnier and Egan, 2019).
In other cases, RH may be due to undiagnosed secondary hypertension or an unrecognised white coat effect. A fourth drug may be initiated if RH is diagnosed, and adherence and lifestyle interventions have been addressed. If RH persists despite optimised lifestyle and pharmacological interventions, this is referred to as treated RH.
Treatment for resistant hypertension
Alpha blockers e.g., doxazosin, can be introduced as fourth-line drugs for RH. They are adrenoreceptor antagonists, and their mode of action is focused on noradrenaline (norepinephrine), reducing peripheral resistance and facilitating vasodilation, which results in lower BP (Williams et al, 2015). A starting dose of 1 mg of doxazosin is given to reduce the risk of first-dose hypotension, and this can then be increased every 2 weeks as required, up to the usual maintenance dose of 4 mg daily. The maximum daily dose is 8 mg.
Interactions with cytochrome P450 34A drugs, such as clarithromycin and itraconazole, and phosphodiesterase-5 inhibitors, such as sildenafil and tadalafil, should be noted. Side effects include palpitations, chest pain and oedema.
Beta blockers are another option as fourth-line therapy in hypertension, although they will be used as first-line drugs for coronary heart disease and heart failure. The mode of action of beta blockers is via their effect on adrenaline (epinephrine) resulting in reductions in BP and heart rate. Beta blockers also inhibit renin production and reduce cardiac output (Williams et al, 2015). The choice of beta blocker will depend on the presence of co-morbid conditions: in heart failure bisoprolol, nebivolol, cardevilol are prescribed, whereas in cardiovascular disease, atenolol or metoprolol may be preferred.
Beta blockers can be prescribed for hypertension at a low dose, e.g. bisoprolol 5 mg once daily, and titrated up to the usual dose of 10 mg, with a maximum dose of 20 mg. As beta blockers reduce heart rate and BP, both should be monitored. If the individual becomes bradycardic, it may be necessary to reduce the dose or stop the medication. Caution should be exercised when prescribing beta blockers in people with reversible airways disease e.g. asthma, but those with chronic obstructive pulmonary disease (COPD) should not be excluded from treatment with beta blockers – indeed, the NICE heart failure guidelines specifically recommend the prescribing of beta blockers in people with COPD due to their morbidity and mortality benefits (NICE, 2018).
Spironolactone is a mineralocorticoid receptor antagonist (MRA) which has a diuretic action due to its ability to block the effect of aldosterone, resulting in the loss of sodium and water and lower BP. It has been shown to be superior to bisoprolol and doxazosin as a fourth-line drug for resistant hypertension (Williams et al, 2015). It should only be prescribed if potassium levels are 4.5 mmol/L or below, as it can increase potassium levels when taken. Spironolactone is initiated at a dose of 25 mg once daily and then based on the needs of the individual can be uptitrated to 50 mg or 100 mg.
Monitoring should include reviewing renal function, potassium and sodium within a month of starting treatment, repeating as necessary for each individual. Hyperkalaemia is one of the key potential side effects of spironolactone and is linked with the risk of acute kidney injury, particularly in patients on aspirin or other non-steroidal anti-inflammatory drugs. Other side effects of spironolactone include breast tenderness, gynaecomastia and gastrointestinal symptoms (Patibandla et al, 2023).
Hypertension in pregnancy
Most standard medications used to treat hypertension in non-pregnant individuals (ACE inhibitors, angiotensin receptor blockers, thiazide diuretics) are contraindicated in pregnancy, so NICE has produced guidance on managing hypertension in pregnancy using more appropriate therapies including labetalol, nifedipine and methyldopa (NICE, 2019b, updated 2023). Non-medical prescribers treating pregnant women should be competent to do so and should always ensure that the midwife and doctor responsible for their care is aware of any new diagnosis and treatment.
Summary
Hypertension, which refers to persistently raised arterial blood pressure, may present as primary (essential) or secondary hypertension. Comparing home and blood pressure readings can identify white coat hypertension and can help to avoid over-treatment. Wherever the BP is measured, correct techniques should be employed. Resistant hypertension is said to be present when the BP is not at target despite optimal lifestyle and pharmacological interventions.
National and international guidelines can be used alongside guidance on holistic prescribing practice to ensure that medication is prescribed appropriately and tailored to the individual, taking into account indications, contraindications, patient preference and side effects.
Key Points
- Primary (essential) hypertension refers to the presence of high blood pressure that is most likely the result of ageing or lifestyle factors such as obesity and is not linked to other underlying disease
- Although the risk of postural hypotension has been noted, it is still important to diagnose and treat hypertension in older people
- Calcium channel blockers act primarily as vasodilators. NICE states that they are first-line for people aged 55 and above as the vasodilatory action is more likely to reduce BP effectively in this age group
- Comparing home and blood pressure readings can identify white coat hypertension and can help to avoid over-treatment. Wherever the BP is measured, correct techniques should be employed
CPD reflective questions
- How does type 2 diabetes or ethnicity influence prescribing in hypertension?
- Summarise the mode of action of angiotensin receptor blockers and contrast this with ACE inhibitors
- What advice would you give to patients starting on beta blockers about possible side effects?
- What considerations should be given to monitoring people who have been prescribed spironolactone?