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The management of hypertension in primary care: updated guidance from NICE
Volume 17 Number 1
September 2006

Part 2 — An overview of the management of hypertension         

Introduction
What is hypertension and why is it important?
How should BP be measured?
Ambulatory BP monitoring (ABPM)
Cardiovascular risk and preventative measures
What are treatment thresholds and targets for BP?
Lifestyle interventions
Drug treatment of hypertension
Treatment from the patient’s perspective
Key points for PCTs and prescribers
References

 Introduction

This section of the Bulletin provides an update on the management of hypertension following publication of MeReC Briefing No. 29 on this topic in April 2005 and issue of the updated NICE clinical guideline CG034 in June 2006 (see Part 3 for a review and critique of the revisions in the updated NICE guideline).

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What is hypertension and why is it important?

Cardiovascular disease (CVD) accounts for 30% of all deaths and for four million hospital bed-days annually in England and Wales.¹  Hypertension is one of the major modifiable risk factors for CVD. The co-existence of other modifiable risk factors (e.g. elevated cholesterol, smoking, impaired glucose metabolism) and non-modifiable risk factors (e.g. old age, history of CVD, male gender) dramatically increases the CVD risk associated with any given blood pressure (BP).^2–4

Any definition of hypertension is arbitrary.⁵ Consensus from published guidelines is that hypertension is defined at a BP of >140/90mmHg (i.e. either systolic BP >140mmHg or diastolic BP >90mmHg). Approximately 40% of the adult population of England have a BP of 140/90mmHg or more, with the proportion increasing with age.¹ This results in an estimated 400 GP consultations for hypertension per 2000 list patients per year.¹

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How should BP be measured?

Health care professionals who take BP measurements need adequate initial training and periodic review of their performance, as measurement technique can significantly affect recordings.^1,6 An outline of how BP should be measured by auscultation is provided in Panel 1. The BP measuring devices that are used can also significantly affect recordings. Therefore, devices must be properly validated.⁶ A list of those BP measuring devices that meet BHS (British Hypertension Society) validation criteria are available at www.bhsoc.org/blood_pressure_list.stm. Devices must be properly maintained and regularly recalibrated according to the manufacturers' instructions.⁶ The Medicines and Healthcare products Regulatory Agency (MHRA) has recently issued ‘Top Ten Tips’ for measuring BP.⁷ This is outlined in Panel 2.

BP is inherently labile. Individual readings are influenced, for example, by time of day, posture, emotions, talking, exercise, drugs, meals, etc.¹ Given this, and the potential consequences of misdiagnosis, several readings need to be taken before a diagnosis of hypertension can be made. NICE recommends that recordings should be taken at the beginning and end of each of at least three separate, monthly clinic visits in a standardised environment.^1,6 However, patients with more severely raised BP should be re-evaluated more urgently.^1,6 In patients without existing CVD, if raised BP persists after the third clinic visit, a full assessment of CVD risk (see below) should be used to inform discussions about care options. The average of the recorded BP readings should be used in the risk assessment.

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Ambulatory BP monitoring (ABPM)

Evidence is limited on the degree to which ABPM can be used to determine cardiovascular (CV) prognosis.¹ Potential uses of ABPM include eliminating white coat hypertension, investigating treatment resistant patients, identifying nocturnal hypertension, resolving unusual BP variability in clinic measurements, and evaluating hypotension.^8,9 Use should be targeted to those patients where additional information obtained by ABPM may lead to a change in the patient's management.¹ Routine use of automated ABPM or home monitoring devices in primary care is not currently recommended because their value has not been adequately established.⁶

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Cardiovascular risk and preventative measures

For those people with persistent hypertension but without existing CVD, a formal assessment of their CVD risk should be carried out, using a validated risk assessment tool, as an aid to deciding when treatment is necessary. The BNF contains the Joint British Societies (JBS) CV risk prediction charts. These charts, and their predecessors, which were based on coronary heart disease (CHD) risk, have been widely used in the UK, although there are accepted limitations (see BNF for details).¹⁰ Other risk factors not included in the CVD risk prediction charts should be taken account of in assessing and managing a person’s overall CVD risk. Abdominal obesity, impaired glucose regulation, raised fasting triglyceride levels, and a family history of premature CVD, are some of the other factors that can influence CVD risk.¹¹ In some ethnic groups, the risk charts can underestimate, or sometimes overestimate, CVD risk because they have not been derived from these populations.¹¹ For example, in people originating from the Indian subcontinent it is reasonable to assume that CVD risk is about 1.5 times higher than predicted from the charts.¹⁰ A CVD risk score can be approximated from a CHD risk score by multiplying by 4/3 (i.e. a CHD risk of 15% is equivalent to a CVD risk of 20%).⁶

Treating hypertension should not be viewed in isolation and other interventions, such as statins and aspirin, should be considered, where appropriate, based on people’s history of CVD or an assessment of their CVD risk.

The NICE appraisal of statins states that, after discussing the risks and benefits of treatment with patients, statins are recommended:¹²

• for adults with clinical evidence of CVD (i.e. secondary prevention), and,
• as part of the management strategy for the primary prevention of CVD for adults who have a 20% or greater 10-year risk of developing CVD.

Both NICE and BHS guidelines recommend aspirin 75mg daily for all people with established CVD.¹³ Thresholds for using low-dose aspirin to prevent CV events in people without existing CVD are difficult to define. These people are at lower risk of a serious vascular event than those with existing disease, and for many such people the risk of adverse effects (such as major bleeding) may outweigh the benefits of taking aspirin. The BHS recommend aspirin 75mg daily for primary prevention in patients with hypertension aged >50 years with BP controlled to <150/90mmHg and either target organ damage, diabetes mellitus, or 10-year CVD risk of >20%.²

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What are treatment thresholds and targets for BP?

Thresholds for treatment of raised BP consider overall CVD risk, in addition to the absolute BP level. The greater the CVD risk, the greater the potential to benefit from treatment.¹ The thresholds and targets recommended in the NICE guidelines on hypertension⁶ and diabetes^14,15 are listed in Table 1. The target BPs set out in the Quality and Outcomes Framework of the new General Medical Services contract¹⁶  (<150/90mmHg in non-diabetic hypertensive patients, <145/85mmHg in diabetic hypertensive patients) differ from those advised for optimal clinical management and can be considered as minimum standards for audit.

The evidence base on optimal target pressures for both systolic BP (SBP) and diastolic BP (DBP) remains incomplete. Target BPs are based predominantly on data from two landmark studies: the Hypertension Optimal Treatment (HOT) trial¹⁷ and UKPDS in patients with diabetes.¹⁸ See MeReC Briefing No. 29, April 2005 for details.

For people with raised BP, any reduction in BP towards the target is beneficial. However, the intensity of treatment should be guided by patients, balancing their acceptance of treatment (concordance, polypharmacy, side effects, quality of life) with the desired reduction in BP. A stepped approach as recommended for drug treatment in the NICE guideline⁶ can be used to achieve target, titrating up dose, where appropriate, and adding additional drugs if necessary. Switching to alternative drugs from another class may also be appropriate for some patients (see later section on drug treatment).

Decisions on treatment goals should be reached in full discussion with patients, since the trial evidence does not support one target BP. The aim should be to achieve as great a reduction in BP towards the target as is acceptable to the individual patient.

In trials using stepped medication regimens, 50–75% of patients achieved a BP target of <140/90 mmHg, and around a half of patients required more than one drug.⁶ Despite differences between trial settings and every day general practice, this also suggests that a sizeable minority of patients may be able to achieve target BP with monotherapy.

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Lifestyle interventions

A healthier lifestyle, by lowering BP and CVD risk, may reduce, delay or remove the need for long-term drug therapy in some patients.¹ As such, all hypertension guidelines recommend that lifestyle interventions should form an integral part of the management of high BP, either alone or in addition to drug therapy, depending on how severely BP is raised.

Trials of lifestyle interventions vary widely in size, methodology, duration and quality, and unfortunately, tend to report reductions in BP, rather than patient orientated outcomes such as changes in morbidity or mortality. Combinations of lifestyle interventions may achieve greater reductions in BP than single interventions for some people. About a quarter of patients receiving multiple lifestyle interventions were estimated to achieve a reduction in systolic BP of 10mmHg or more in short-term trials up to one year.¹ However, lifestyle interventions can be difficult to achieve for many. Patients need to be highly motivated, require regular follow-up and considerable support to maintain change over the longer-term.¹

Key lifestyle advice for patients, and the associated changes in BP that have resulted from adherence in trials, are given in Table 2. MeReC Briefing No. 19, September 2002 provides a fuller discussion of the effects of lifestyle measures on hypertension and CVD risk.

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 Drug treatment of hypertension

A range of effective antihypertensive drugs from different pharmacological classes can be considered for the treatment of hypertension. On an individual patient basis, some drugs may be more effective and/or have a more tolerable side-effect profile than others.

Of paramount importance for reducing CVD risk is the degree of BP reduction achieved. Although there may be some benefits for particular drug classes in specific patient groups, in general, there is little evidence of clinically significant, drug-specific effects to distinguish the efficacy of drugs within or between classes when their BP lowering effect is taken into account. Therefore, choice of antihypertensive should be based on individual patient factors (e.g. comorbidities, ethnic origin), side-effect profiles, and costs.

What does the updated NICE guideline recommend?
The updated NICE guideline on hypertension was issued in June 2006 and contains a revised section on drug treatment.⁶ Recommendations for other aspects of the management of hypertension remain unchanged from the 2004 guideline.¹⁹

Recommendations for drug treatment were made following a systematic review of randomised controlled trial (RCT) data and a health economic analysis.²⁰ In view of the limitations and uncertainties of the clinical evidence and economic analysis, many of the recommendations were based on pathophysiological grounds and expert opinion/consensus.

The systematic review of RCTs conducted for the NICE review found no difference between the classes of drugs with regard to the risk of death or myocardial infarction (MI).²⁰ However, β-blockers were considered less effective than comparator drugs in reducing the risk of strokes. Thiazide diuretics and calcium-channel blockers (CCBs) were considered the most likely drugs to confer benefits in CV outcomes, except possibly in younger patients.⁶

β-blockers are no longer considered by NICE as an appropriate choice for initial treatment of hypertension, unless there are compelling reasons to use them (e.g. ischaemic heart disease). However, they are an option for younger people, in particular: women of child-bearing potential, patients with evidence of increased sympathetic drive, or patients with an intolerance or contraindications to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-II receptor antagonists (AIIRAs). It is recommended that β-blockers are not combined with a diuretic because of the increased risk of developing diabetes. NICE recommendations for patients already receiving a β-blocker are summarised in Panel 3 .⁶

The economic analysis conducted for the NICE review slightly favoured CCBs, with thiazide diuretics being the next most cost-effective option for drug treatment. CCBs were associated with additional higher costs (NHS and social) of about £12,000–£13,000 per quality adjusted life year (QALY) gained (i.e. a gain of one year of life in good health) compared with thiazide diuretics. This additional cost was considered affordable to the NHS, provided that the cost of CCBs was not more than £105 per year (£8 per 28 days).²⁰

Thiazide diuretics or CCBs are considered by NICE as equal first-line choices for people who are black (i.e. of African or Caribbean descent, not mixed race, Asian or Chinese) or aged 55 years or older. NICE suggests that the choice between thiazide diuretics and CCBs should be made by the clinician and patient, using careful clinical judgement about the patient’s risk of adverse effects and consideration of the patient’s preference.⁶ Prescribers may decide to use diuretics preferentially in view of their lower acquisition costs, unless there are good reasons to do otherwise.

ACEIs are recommended for people younger than 55 years old. Where an ACEI is indicated but not tolerated (e.g. because of cough) an AIIRA is appropriate.⁶

Many patients will require more than one drug to achieve BP control. Where the first-line drug does not adequately control BP, NICE recommends additional drugs should be added in a sequential manner according to the algorithm shown in Figure 1.⁶

The NICE updated recommendations for routine drug treatment follow the A(B)/CD approach previously adopted in the BHS guidelines.² This approach is not supported by large clinical outcome studies, but is based on sound pathophysiological grounds. The theory behind the algorithm is that younger Caucasians (<55 years of age) usually have higher renin levels compared with those who are black (of African descent) or are older (>55 years of age).^1,2 Therefore, drugs that reduce BP by suppressing the renin-angiotensin system (e.g ACEIs/AIIRAs or β-blockers) should be used initially in younger Caucasian patients, and those that don't suppress the renin-angiotensin system (e.g. CCBs or diuretics) should be used in older Caucasian patients and all patients of African descent.^1,2 Omission of β-blockers from the routine treatment algorithm (as previously included in the BHS guidelines) was justified on the basis of the higher risk of developing diabetes when used in combination with a thiazide diuretic.⁶

Where a combination of a diuretic, an ACEI and a CCB is not effective in controlling BP, an α-blocker, a high-dose or an additional diuretic (careful monitoring required), or a β-blocker can be considered. Referral to a specialist should also be considered at this stage.⁶

It is possible that, rather than adding drugs sequentially if patients do not tolerate or respond adequately to the first drug prescribed, switching to a drug from a different class in the first instance could be successful.²¹ However, most international guidelines, including those from NICE, do not recommend this approach specifically ^6,9,22 and, like the A(B)/CD approach, it is not supported by large outcome studies. A small crossover rotation study of 56 patients with hypertension (ages 22–51 years, mean BP 161/98mmHg) found significant variability in response between four different antihypertensive classes (diuretics, β-blockers, CCBs and ACEIs). Only 39% achieved their BP target (<140/90mmHg) on the first drug they received, whereas 73% did so on their best drug.²³

Figure 1: NICE algorithm for the drug treatment of patients with newly diagnosed hypertension6 Click here to return to 'What does the updated NICE guideline recommend?' section Click here to return to 'Panel 3'
A = ACEI (AIIRA if intolerant), C = calcium channel blocker, D = thiazide diuretic † of African or Caribbean descent, and not mixed race, Asian or Chinese ‡ β-blockers are an alternative to A in patients younger than 55 years if A is not tolerated or is contraindicated (including women of childbearing potential)

Several aspects of the drug treatment of hypertension in the updated NICE guideline are unchanged from the previous guideline. BP thresholds and targets for treatment remain the same (see Table 1). Where possible, non-proprietary and once-daily treatment should be prescribed. Prescribers are also advised to provide appropriate guidance and materials about benefits of drugs and possible unwanted side effects in order to help patients make an informed choice.⁶

What about the previous concerns over CCBs?
Results of clinical studies prior to 2000 raised the concern that CCBs increase the risk of CV events independent of their BP lowering effect, compared with other antihypertensives.^24,25 These concerns have largely been alleviated by more recent trials with amlodipine or modified-release (MR) verapamil. In ASCOT,²⁶ INVEST,²⁷ ALLHAT,²⁸ and CONVINCE,²⁹ the incidences of death or major CV events with these CCBs were fewer or no different compared with other classes of drugs. However, CCBs are not as effective as thiazide diuretics in preventing heart failure. For instance, in the ALLHAT study, the risk of heart failure leading to death or hospitalisation was greater over the first year (relative risk [RR] 2.22, 95%CI 1.69 to 2.91, p<0.001) than subsequent years (RR 1.22, 95%CI 1.08 to 1.38, P=0.001) with amlodipine compared with chlortalidone.³⁰ Lisinopril was also associated with an increased risk of heart failure during the first year compared with chlortalidone (RR 2.08, 95%CI 1.58 to 2.74, P<0.001), although there was no significant difference in subsequent years.³⁰

Immediate-release formulations of short-acting dihydropyridine CCBs (e.g. standard-release nifedipine), which are associated with large variations in BP, should be avoided.¹³ Amlodipine, MR nifedipine or MR felodipine are appropriate choices. Rate limiting CCBs (e.g. MR diltiazem or MR verapamil) are an alternative to β-blockers or dihydropyridine CCBs in people with angina, and as an alternative to β-blockers if these are not tolerated post-MI.¹³ There are many branded products of MR CCBs available, which may not have the same clinical effect. To avoid confusion, they should be prescribed by their brand name.¹⁰ Refer to the latest BNF for options, dosing regimens and costs.

What about AIIRAs?
Advice regarding the use of AIIRAs is effectively unchanged in the updated NICE guideline. AIIRAs should only be considered where an ACEI is indicated but not tolerated.^6,31 The most common reason for intolerance is a dry cough, which occurs in about 5–10% of people.³² There is no compelling evidence to suggest that AIIRAs offer any clinical advantage over ACEIs, or that there are differences between individual agents,⁶ and AIIRAs are considerably more costly than ACEIs (see Figure 2 ). There is also insufficient evidence to suggest any synergistic or clinically significant effect of using an ACEI and an AIIRA in combination.^33,34

A meta-analysis of three large RCTs of AIIRAs in patients with hypertension (vs. placebo, atenolol or amlodipine), with follow up for at least two years, suggested that AIIRAs increase the risk of MI (RR 1.12, 95% CI 1.01 to 1.26, P=0.041), but decrease the risk of new-onset diabetes (RR 0.80, 95%CI 0.74 to 0.86, P<0.0001).³⁵ However, other reviews of their use in a range of conditions have failed to identify a significant increased risk of MI relative to other treatments.^36,37

What about α-blockers?
Although α-blockers are effective in reducing BP, there is no evidence that their use prevents clinically important endpoints. In the ALLHAT study, treatment of the doxazosin group was stopped early because of a doubling in the risk of heart failure compared with the chlortalidone group (four-year rates, 8.13% vs. 4.45%; RR, 2.04; 95% CI, 1.79 to 2.32; P<0.001).³⁸ Advice for use of α-blockers is unchanged in the updated NICE guideline; they can be considered as a fourth-line choice.⁶

What about patients with diabetes and hypertension?
Lowering BP reduces CV complications and progression of renal dysfunction,^2,39 and is of paramount importance alongside other preventative measures (stopping smoking, lipid lowering, aspirin, glucose control) in patients with type 1¹⁵ and type 2 diabetes.⁴⁰ NICE guidelines recommend lower BP targets for patients with diabetes than for patients without diabetes (see Table 1).

Neither the NICE 2004 hypertension guideline¹⁹ nor the 2006 update⁶ considered treatment of patients with diabetes. The most recent NICE guidelines for management of BP in patients with type 2 diabetes are from 2002,¹⁴ and did not consider the more recent large outcome studies that included a large population of people with diabetes, such as ALLHAT and ASCOT. A revision of the NICE guideline on management of type 2 diabetes is expected in 2008. The 2002 type 2 diabetes guideline recommends consideration of either an ACEI or AIIRA, a β-blocker or a thiazide diuretic as first-line treatment for patients with type 2 diabetes without renal complications. CCBs are considered a second-line or combination option.¹⁴ The NICE 2004 type 1 diabetes guideline recognises that multiple drug therapy may be necessary to control BP, and recommends thiazide diuretics as the first-line treatment unless an ACEI/AIIRA is already being taken for nephropathy.¹⁵

Based on more recent evidence, the use of an ACEI (or AIIRA if not tolerated) or thiazide diuretic first-line still seems reasonable in people with diabetes. However, the use of a β-blocker as a first-line treatment for hypertension in patients with diabetes would now seem inappropriate, unless there are compelling indications such as ischaemic heart disease.

The Blood Pressure Lowering Treatment Trialists' Collaboration meta-analysis considered 27 trials that included 158,709 participants (33,395 with diabetes). It found that total major CV events were reduced to a similar extent in individuals with or without diabetes by regimens based on a diuretic or β-blocker (combined comparator group), an ACEI, an AIIRA, or a CCB.⁴¹ The ALLHAT study, which included over 13,000 people with diabetes, provides support for the first-line use of diuretics in this population. Chlortalidone, amlodipine and lisinopril were all similarly effective in reducing CV events and mortality in patients with diabetes. However, in patients with impaired fasting glucose, the incidence of the primary endpoint (fatal CHD or non-fatal MI) occurred in a significantly higher proportion of patients randomised to amlodipine compared with those randomised to chlortalidone (RR 1.73, 95%CI 1.10 to 2.72, P=0.01). Heart failure was more common in patients with diabetes assigned to amlodipine compared with chlortalidone (RR 1.39, 95%CI 1.22 to 1.59, P=0.001).⁴²

ACEIs may have specific renoprotective actions in patients with incipient or overt type 1 diabetic nephropathy, and are recommended as initial therapy for hypertension for these patients in both the BHS and NICE guidelines.^2,15 Although ACEIs have an antiproteinuric action and delay progression from microalbuminuria to overt nephropathy, it is less clear whether they have specific renoprotective action beyond BP reduction in overt nephropathy complicating type 2 diabetes.^2,43 However, in reality most patients with diabetes will require more than one agent to achieve their BP target, and this will normally include an ACEI.³⁹ The use of ACEIs (or AIIRAs if not tolerated) is recommended as a first-line treatment for patients with microalbuminuria and type 2 diabetes in NICE guidelines.¹⁴

BP control is also important in preserving the renal function of people with non-diabetic kidney disease.² Recent UK guidelines for the management of chronic kidney disease in adults from the Royal College of Physicians and the Renal Association (RCP/RA) recommend thresholds and targets based on whether or not the urine protein/creatinine ratio (PCR) is above or below 100mg/mmol (approximately 1g urinary protein/24 hours).⁴⁴

• Urine PCR<100mg/mmol — Initiate treatment at 140/90mmHg with a target of 130/80mmHg
• Urine PCR>100mg/mmol — Initiate treatment at 130/80mmHg with a target of 125/75mmHg

ACEIs or AIIRAs are recommended for these patients together with appropriate monitoring of serum creatinine and potassium levels (see the full RCP/RA guideline for more details).⁴⁴
 

What about black patients/ethnic minorities?
The updated NICE guideline recommends using a thiazide diuretic or CCB first-line in black people with hypertension.⁶ The pathophysiology of hypertension differs in black adults compared to south Asians and Caucasians, and ACEIs/AIIRAa and β-blockers are generally less effective as monotherapy.⁴⁵ 

A systematic review of 26 RCTs found that β-blockers did not significantly reduce systolic BP compared with placebo (weighted mean difference –3.53mmHg, 95%CI, –7.51 to 0.45mmHg) in black patients, and ACEIs were no more effective than placebo in achieving diastolic BP goals (RR 1.35, 95%CI 0.81 to 2.26).⁴⁶ Subgroup analyses of the ALLHAT study suggested that the lisinopril-based regimen was associated with a higher incidence of stroke (RR 1.40, 95%CI 1.17 to 1.68) and CV events (RR 1.19, 95% CI 1.09 to 1.30) than the chlortalidone-based regimen in black patients, whereas there were no significant differences in non-blacks (stroke: RR 1.00, 95%CI 0.85–1.17; CV events: RR 1.06 (95% CI, 1.00 to 1.13).⁴⁷ In the LIFE study, which included patients with hypertension and left ventricular hypertrophy (LVH), the risk of CV death, stroke, or myocardial infarction (MI) was greater in the losartan group compared with the atenolol group (hazard ratio [HR] 1.67; 95%CI 1.04 to 2.67) in black patients whereas it was lower in non-black patients (HR 0.83, 95% CI 0.73 to 0.94).⁴⁸

What about patients with isolated systolic hypertension (ISH)?
NICE considered that there was insufficient evidence to treat patients with ISH any differently from other patients with raised systolic and diastolic BP.⁶ A meta-analysis of three RCTs in patients with ISH identified a significant reduction in the incidence of stroke (odds ratio [OR] 0.62, 95%CI 0.51 to 0.77) and MI (OR 0.74, 95%CI 0.61 to 0.91) for diuretic- or CCB-based antihypertensive regimens compared with placebo, but no difference in mortality rates.²⁰ A subgroup analysis of patients with ISH in the LIFE study found that a losartan-based regimen was associated with a reduced incidence of stroke (RR 0.60, 95%CI 0.38 to 0.92) and a lower CV mortality rate (RR 0.54, 95%CI 0.34 to 0.87) compared with an atenolol-based regimen.⁴⁹

What about very elderly people?
The absolute benefits of treating hypertension in older people are greater because of their higher absolute risk of suffering a CV event. However, the benefits of treatment have to be balanced against the possible hazards, e.g. postural hypotension and falling. People over the age of 80 are poorly represented in clinical trials, therefore evidence of effectiveness is less certain. A meta-analysis of data from seven studies, which included 1670 participants aged 80 years or older, suggested that treatment prevented 34% (95% CI 8% to 52%) of strokes, and rates of major CV events and heart failure were significantly decreased by 22% and 39%, respectively.⁵⁰ However, there were no effects on CV or all-cause mortality. In the absence of good evidence to the contrary, patients over the age of 80 years should be treated for hypertension in the same way as other adults.⁶

What about adverse effects?
Antihypertensive drugs are all associated with a range of class-specific adverse effects, which can influence choice and limit their use in some patients. A 2003 Health Technology Assessment review quantified the adverse events reported in 354 placebo-controlled trials of antihypertensives.⁵¹ Significantly more patients suffered one or more drug-related symptoms, relative to placebo, when taking thiazide diuretics (difference 9.9%, 95%CI 6.6% to 13.2%), β-blockers (difference 7.5%, 95%CI 4.0% to 10.9%), or CCBs (difference 8.3%, 95%CI 4.8% to 11.8%). However, this was not the case for ACEIs (difference 3.9%, 95%CI –0.5% to 8.3%) or AIIRAs (difference 0.0%, 95%CI –5.4% to 5.4%). There were no serious metabolic consequences of using any of the drugs at standard doses, and use of diuretics, β-blockers, and CCBs were considered safe to use without routine biochemical monitoring. Measurement of potassium and creatinine before and after taking ACEIs or AIIRAs was also considered as probably overcautious. In most cases, symptoms were not sufficient to stop taking the drugs and were reversible if this was done. The differences in the proportions of patients who discontinued treatment due to adverse effects (treatment group minus placebo) were: thiazide diuretics 0.1%, β-blockers 0.8%; ACEIs 0.1%, AIIRAs –0.2%, and CCBs 1.4%.⁵¹ The differences from placebo were only significant for CCBs and β-blockers.

Another systematic review of 190 studies comprising 409 treatment groups (28,922 patients in total) of individual drugs for the treatment of essential hypertension estimated the frequency of discontinuation due to adverse effects as: CCBs 6.7%; α-blockers 6.0%; ACEIs 4.7%; β-blockers 4.5%; placebo 4.3% and AIIRAs and diuretics both 3.1%.⁵²

Cost impact of the updated NICE guideline
To accompany the updated NICE guideline, NICE have produced a costing report and template (an Excel spreadsheet) to help health communities assess the likely local impact of implementing the NICE guideline.^53,54 If the guideline is implemented in full, which may take several years, it is predicted that the additional annual cost of providing antihypertensive drugs according to the revised NICE algorithm in England would be £58 million. However, in the long-term, the costing report estimates that these additional costs would be offset by an annual cost saving to the NHS of £280 million due to reductions in the incidence of stroke and ischaemic heart disease; a net saving of £222 million per year.⁵⁴

Although the best available data was used for producing these national cost estimates, they are based on a number of assumptions. Current and future drug usage patterns are based on a consensus of clinical experts, and it is assumed that that new patients would be prescribed the cheapest drug within the class that is appropriate, whereas existing patients would continue on their current drug. The template allows health communities to estimate the local cost impact by inputting figures based on their local population characteristics and drug usage patterns. The costing template can be downloaded from the NICE website.⁵³

Drug costs and other information
Refer to the Summaries of Product Characteristics for more detailed information on adverse effects, dosing, precautions, and contraindications (www.medicines.org.uk).

NHS costs of some selected antihypertensive drugs at a range of typical doses are shown in Figure 2 .⁵⁵

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Treatment from the patient’s perspective

Individuals will differ in their attitudes to risk, the value they place on treatment and the side effects they are willing to accept. These individual patient preferences should be identified and considered when recommending treatments.  Many patients may reasonably reject drug treatment for mild hypertension based on their own values.

A survey of 587 patients with hypertension receiving treatment at one GP surgery identified that 80% of patients had reservations about taking their antihypertensive medication (e.g. preference for non-drug measures to lower BP, anxiety about side effects that the treatment might have in the long run). Around a third of patients also wondered whether treatment was still necessary.⁵⁸ This reinforces the need to involve patients fully in treatment decisions on an ongoing basis. NICE guidelines recommend that all patients should have an annual review of care to monitor BP, provide support, and discuss lifestyle, symptoms and medication.⁶

It is estimated that 50–80% of patients with hypertension do not take all of their prescribed medication.¹ Reasons include the asymptomatic nature of hypertension, the need for long-term treatment, complex drug regimens, poor instructions, and disagreement about the need for treatment.¹ Doctors and other heath professionals should consider non-adherence to medication when evaluating a patient with poor BP control.⁵⁹ Understanding a patient’s reasons for not taking their medication is important for implementing effective strategies to improve the management of their hypertension.¹

The adherence rates to antihypertensive medication are significantly higher with once-daily dosing compared to twice-daily dosing (93% vs. 87%) or multiple-daily dosing (91% vs. 83%).⁶⁰ and, where possible, treatment with drugs taken only once daily should be recommended.⁶

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Key points for PCTs and prescribers

See Panel 4 .

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References

1. North of England Hypertension Guideline Development Group. Essential hypertension: managing adult patients in primary care. Evidence-based Clinical Practice Guideline; August 2004. Accessed from www.nice.org.uk on 22/08/06
2. Williams B, Poulter NR, Brown MJ, et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society 2004—BHS IV. J Hum Hypertens 2004;18:139–85
3. Padwal R, Straus SE, McAlister FA, et al. Cardiovascular risk factors and their effects on the decision to treat hypertension: evidence based review. BMJ 2001;322:977–80
4. Jackson R, Lawes CMM, Bennett DA, et al. Treatment with drugs to lower blood pressure and blood cholesterol based on an individual's absolute cardiovascular risk. Lancet 2005;365:434–41
5. Guidelines Subcommittee. 1999 World Health Organization - International Society of Hypertension guidelines for the management of hypertension. J Hypertension 1999;17:151–183
6. National Institute for Health and Clinical Excellence. Hypertension: management of hypertension in adults in primary care (partial update of NICE clinical guideline 18). Clinical Guideline 34. June 2006. Accessed from www.nice.org.uk on 22/08/06
7. Medicines and Healthcare products Regulatory Agency. Medical Device Alert MDA/2006/037. Blood pressure monitors and sphygmomanometers. 13th July 2006. Accessed from www.mhra.gov.uk on 25/07/06
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