Clinical Focus

An update on hypertension for nurse prescribers

Helen Williams
Abstract
In 2011, National Institute for Health and Clinical Excellence (NICE) guidance for hypertension endorsed the use of ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension. When ABPM is not available, home blood pressure monitoring (HBPM) is preferred over clinic blood pressure readings. The diagnostic threshold for hypertension using ABPM or HBPM is any blood pressure of 135/85 mmHg or higher. Once diagnosed, patients should be offered lifestyle advice, and, if appropriate, drug therapies, aiming to control blood pressure to lower than 140/90 mmHg. A revised treatment algorithm recommends angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or calcium channel blockers as first- and second-line therapy options. Ensuring appropriate ongoing monitoring as well as identifying and addressing non-adherence are key issues.

There are two potential solutions to this issue: Ambulatory BP monitoring (ABPM) Home BP monitoring (HBPM). Ambulatory BP monitoring ABPM is a non-invasive method of obtaining BP readings over 24 hours, while the patient goes about their normal activities of living. There is substantial evidence that ABPM is superior to clinic BP in predicting future cardiovascular events and target organ damage (Clement, 2003; Hodgkinson, 2011). With ABPM, BP readings are taken half hourly during the day and hourly overnight. If the average of daytime BP readings is greater than 135/85mmHg, hypertension is diagnosed (Box 1). There are technical issues relating to the use of ABPM, and the clinician must ensure that the daytime average BP is based on eight or more successful daytime BP readings. ABPM is favoured by NICE guidance, as it is the most cost-effective strategy compared with clinic BP monitoring or HBPM.

ew National Institute for Health and Clinical Excellence (NICE) guidance for hypertension (CG127) was published in August 2011. The guidance brought significant changes to both diagnosis and the management of hypertension (NICE, 2011). This article discusses the rationale for these changes to update prescribers.

Box 1. BP thresholds for diagnosis of hypertension

Stage 1 hypertension

Diagnosis

Traditionally, diagnosis of high blood pressure (BP) has relied on serial checks of clinic BP over a 23-month period, with hypertension confirmed if BP remains persistently raised over 140/90 mmHg. This method of diagnosis has significant limitations because the BP measured for an individual patient in a clinic setting may not reflect their BP in day-to-day life. The primary concern is that BP may be artificially raised in a substantial proportion of people when checked in the clinic setting; therefore, hypertension may be being overdiagnosed, resulting in unnecessary treatment.
Helen Williams is a Consultant Pharmacist for Cardiovascular Disease at South London Cardiac and Stroke Network and a member of the NICE Hypertension Guideline Development Group Email: helen.williams11@nhs.net

Clinic BP 140/90 mmHg or higher; and ABPM or HBPM average 135/85 mmHg
Stage 2 hypertension

Clinic BP 160/100 mmHg; and ABPM or HBPM daytime average 150/95mmHg

Severe hypertension

Clinic BP 180 mmHg; or Clinic diastolic BP 110 mmHg

ABPM: ambulatory blood pressure monitoring; BP: blood pressure; HBPM: Home blood pressure monitoring. From: NICE (2011)

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Non-pharmacological management
All patients should be offered lifestyle advice to address cardiovascular risk factors, including smoking cessation. Dietary modification, including reducing salt intake, increased exercise, weight loss, and alcohol moderation can significantly lower BP (Table 1). In patients with stage 1 hypertension and low or moderate calculated CV risk (<20% over 10 years), non-pharmacological management of hypertension is the preferred option.

Box 1. BP thresholds for initiating drug therapy

Treat if:

Stage 1 hypertension: BP 140/90 mmHg, where there is: evidence of target organ damage, diabetes, renal disease, or the calculated CV risk is high (20% over 10 years) Stage 2 hypertension: BP 160/100 mmHg
BP: blood pressure. From: NICE (2011)

Pharmacological management

Home BP monitoring For HBPM, the patient needs to have access to a validated BP machine that has been calibrated. The patient takes BP readings morning and evening for 7days and records the results. For each BP recording, two consecutive measurements should be taken at least 1 minute apart with the person seated. The first days results should be discarded and an average of the results of all of the other readings used to assess the presence or absence of high BP. As with ABPM, for HBPM, the threshold for diagnosis of hypertension is BP greater than or equal to 135/85 mmHg (NICE, 2011).

In the past, there has been a tendency to initiate drug therapy in all patients with hypertension. More recently, this has been further driven by pressure to achieve the targets defined in the quality and outcomes framework, but this approach is not evidence based (NHS Employers and British Medical Association, 2012). Drug therapy should only be initiated in line with criteria from NICE (Box 2). Essentially, drug therapy should be considered for all patients with stage 2 hypertension, but only for selected high risk patients with stage 1 hypertension. Target organ damage is evidenced by damage to the heart, such as left ventricular hypertrophy, angina, or prior myocardial infarction and heart failure; or brain, such as stroke or transient ischemic attack; or the presence of chronic kidney disease, peripheral arterial disease, or retinopathy. Drug choice A NICE treatment algorithm outlines medication choice for the treatment of hypertension (see NICE, 2011). NICE recommends different treatment choices at step 1, based on age and ethnicity. ACEIs and ARBs Angiotensin-converting enzyme inhibitors (ACEIs) or low-cost angiotensin-II receptor blockers (ARBs)

Assessing cardiovascular risk

Full cardiovascular risk assessment using an approved cardiovascular (CV) risk calculator, such as modified Framingham or QRisk, should be undertaken for all patients, except where a diagnosis of CV disease or diabetes is present or there is evidence of target organ damage. Patients with a 10-year CV disease risk of 20% or more require more intensive BP lowering interventions (Box 2).

Table 1. Impact of dietary modifications on BP

Modification
Weight loss DASH (Dietary Approaches to Stop Hypertension)-type diet Reduced salt intake Physical activity

Recommendation
Maintain normal body weight Consume a diet rich in fruits, vegetables, and low-fat dairy products with reduced saturated and total fat Reduce daily dietary sodium intake Regular aerobic physical activity (at least 30 min/day, most days of the week) Limit consumption to two drinks/day in men and one drink/day in women and lighter-weight patients

Approximate systolic BP reduction (mmHg)

520 per weight loss of 10 kg 814

28 49

Moderation of alcohol intake

24

BP: blood pressure. From: Williams et al (2004)

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should be used first line in younger patients (age <55years) and at step 2, in combination with a calcium channel blocker, in all patients. Since the previous NICE guidance, three new head-to-head, randomised, controlled trials have demonstrated that ARBs provide equal BP lowering efficacy to ACEIs, but with fewer drug withdrawals. Some ARBs have also become more cost effective than they have been previously owing to patent expiriescurrently, losartan, candesartan, irbesartan, and valsartan are available generically, but not all have achieved cost parity with ACEI therapy. However, since publication of the NICE 2011 guidance, a meta-analysis of over 158998 patients in 20 cardiovascular mortality/morbidity trials concluded that overall, reninangiotensinaldosterone inhibition was associated with a 5% reduction in all-cause mortality (P=0.032) and a 7% reduction in cardiovascular mortality (P=0.018). The observed treatment effect resulted entirely from the class of ACEIs, which were associated with a significant 10% reduction in all-cause mortality (P=0.004), whereas no mortality reduction could be demonstrated with ARB treatment (van Vark, 2012). Based on this evidence, ACEI therapy should be used in preference to an ARB, wherever tolerated. The only exception to this is people of black African and Caribbean family origin, owing to an increased risk of angioedema with ACEI therapy in this group. Finally, there is a clear recommendation from NICE that ACEI and ARB therapy should not be combined for the treatment of hypertension, as there is little evidence of improved BP lowering effect, but a clear increase in the risk of adverse effects. Calcium channel blockers A calcium channel blocker, such as amlodipine, is recommended at step 1 for older people and those of black African or Caribbean origin family. Previous iterations of the NICE (2011) guidance recommended either a thiazide diuretic or a calcium channel blocker at this step, but this version gives preference to calcium channel blocker in most circumstances. This recommendation is based on an improved costeffectiveness profile for calcium channel blockers due to patent expiries over recent years. In addition, there is evidence that at step 2, the combination of an ACEI or ARB with a calcium channel blocker is more effective at protecting against myocardial infarction compared with an ACEI or ARB plus a diuretic (Jameson, 2008). Diuretic therapy Diuretics are now primarily recommended for use at Step 3 of the treatment algorithm in patients where BP remains uncontrolled despite treatment with an ACEI or low-cost ARB and a calcium channel blocker. However, diuretic therapy can also be considered at
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step1 as an alternative to calcium channel patients at high risk of oedema or heart failure. In addition to changing the position of diuretic therapy within the treatment algorithm, the NICE 2011 guidance also made recommendations over which diuretic should be used. Previously, bendroflumethazide had been used routinely in the UK as the thiazide diuretic of choice, but it is rarely used in the rest of the world. In addition, we have tended to prescribe low doses of bendroflumethiazide, such as 2.5mg daily, to minimise electrolyte and metabolic disturbances, but there is no data that this dose has an impact on CV outcomes. All outcome studies with bendroflumethiazide used a higher dose of 10 mg daily. In contrast, there are outcomes data to support the use of low-dose indapamide or chlortalidone, both of which are thiazide-like diuretics. On this basis, NICE recommends that new patients should be initiated on a thiazide-like diuretic, but do not recommend switching well-controlled patients from bendroflumethiazide. Indapamide 2.5mg daily is preferred owing to cost-effectiveness reasons. At the time of writing, chlortalidone is only available in high-strength tablets, which are more suitable when higher diuretic doses are required, as in step 4 of the treatment algorithm. Monitoring drug therapy Clinic BP readings should be used to monitor efficacy of drug treatment, except where there was a significant discrepancy between clinic readings and ABPM/ HBPM readings at diagnosis, indicating white coat hypertension. In such cases, ABPM or HBPM may be used for monitoring BP throughout treatment. Once drug therapy has been initiated, patients should be treated to achieve a clinic BP of <140/90mmHg, except for older patients in whom a target of <150/90 mmHg is recommended (Box 3). Until recently, there has been little data to determine the treatment targets for older adults (age 80 years), as they have been poorly represented in clinical trials and epidemiological data have suggested that aggressive BP lowering in this patient group may increase mortality (Langer, 1993). HYVET (Hypertension in the Very Elderly Trial) specifically sought to investigate the treatment of high BP in older people and demonstrated that treating older patients to a BP target of 150/80mmHg was safe and associated with significant reductions in total mortality, stroke, and heart failure (Beckett, 2008).

Managing resistant hypertension

Resistant hypertension is thought to affect 500000people in the UK, and is likely to increase as we see a greater proportion of older patients with comorbidities. There is a paucity of clinical data on which to base recommendations at step 4 of the

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Box 3. BP treatment targets

Treat to achieve a clinic BP of:

<140/90 mmHg if <80 years old <150/90 mmHg if 80 years old

If ABPM or HBPM used to monitor BP, treat to achieve:

the increased risk of stroke, heart attack, and kidney dysfunction, and the benefits of drug therapy. Patients should be encouraged to be actively involved in decisions about their care, and discuss any concerns they may have. There is no single intervention to address nonadherence, but NICE guidance on adherence suggests that the following should be considered: Address any beliefs and concerns the patient has about their medicines Use interventions to overcome practical problems if there is a specific need; interventions might include: suggesting patients record their medicine-taking, encouraging patients to monitor their condition, simplifying the dosing regimen, using alternative packaging, and using a multi-compartment medicines system Identify if side effects are a problem and discuss benefits, side effects, and long-term effects as well as how the patient would like to deal with side effects: consider adjusting the dosage, switching to another medicine, and other strategies, such as changing the timing of medicines Ask if prescriptions costs are a problem and consider options for reducing costs, such as a prepayment certificate. More information can be found in NICE (2009) CG76 medicines adherence guidance at: www.nice.org. uk/nicemedia/live/11766/42891/42891.pdf

<135/85 mmHg if <80 years old <145/85 mmHg if 80 years old

ABPM: ambulatory blood pressure monitoring; BP: blood pressure; HBPM: Home blood pressure monitoring. From: NICE (2011)

treatment algorithm. The best available evidence supports the use of low-dose spironolactone which reduces BP in resistant hypertension, but has no CV outcomes data. Patients prescribed spironolactone for hypertension will need close monitoring due to the risk of developing painful gynaecomastia, hyperkalaemia, and renal dysfunction during treatment. Other options where spironolactone is unsuitable are a higher dose thiazide like diuretic, such chlortalidone 50 mg daily, an alpha-blocker, such as doxazocin, or a beta-blocker, such as bisoprolol.

Adherence issues

Adherence to drug therapy is key to successful treatment of hypertension. For most patients, having a high BP is asymptomatic, and this can affect motivation to initiate and/or persist with drug therapyespecially if the drugs cause adverse effects, such as ankle swelling with calcium channel blockers or cough with an ACEI. Care should be taken to ensure patients fully understand the consequences of high BP, such as

Who to refer?

Urgent referral is warranted for specific patient groups, in particular those with accelerated hypertension (BP usually higher than 180/110 mmHg with signs of

Table 2. Monitoring parameters for commonly prescribed antihypertensive therapies

Drug classes ACEIs Aldosterone antagonists ARBs Direct renin inhibitors Calcium channel blockers Diuretics Parameters Serum creatinine / eGFR / serum potassium / sodium Check within 24 weeks of initiation or dose titration, then at least annually throughout therapy (more frequent renal monitoring is required with aldosterone antagonists) Heart rate (maintain above 55 beats per minute) Serum creatinine / eGFR Serum electrolytes (K+, Mg2+, Na+) / uric acid Check within 24 weeks of initiation or dose titration, then at least annually throughout therapy

ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin-II receptor blockers; eGFR: estimated glomerular filtration rate

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National Institute for Health and Clinical Excellence (2011) NICE clinical guideline 127. Hypertension: Clinical management of primary hypertension in adults. www.nice.org.uk/nicemedia/ live/13561/56008/56008.pdf (accessed 11 January 2013) Satish S, Freeman DH Jr, Ray L et al (2001) The relationship between blood pressure and mortality in the oldest old. J Am Geriatr Soc 49(4): 36774 van Vark LC, Bertrand M, Akkerhuis KM et al (2012) Angiotensinconverting enzyme inhibitors reduce mortality in hypertension: A meta-analysis of randomized clinical trials of reninangiotensin aldosterone system inhibitors involving 158,998 patients. Eur Heart J 33(16): 208897 Williams B, Poulter NR, Brown MJ et al; British Hypertension Society (2004) Guidelines for management of hypertension: Report of the fourth working party of the British Hypertension Society, 2004 BHS IV. J Hum Hypertens 18(3): 13985

papilloedema and/or retinal haemorrhage) or suspected phaeochromocytoma (labile or postural hypotension, headache, palpitations, pallor, and diaphoresis). A specialist referral should be considered for people with signs and symptoms suggesting a secondary cause of hypertension, especially younger people (younger than 40 years) with stage 1 hypertension and no evidence of target organ damage, cardiovascular disease, renal disease, or diabetes, where a more detailed assessment of potential target organ damage is warranted. This is because the current strategy of assessing 10-year cardiovascular risk in such patients will underestimate the lifetime risk of cardiovascular events in these people, and may delay initiation of appropriate therapies. Specialist advice should be sought for patients with hypertension resistant to four anti-hypertensive agents, where the BP is labile or rapidly worsening and in patients with other exacerbating conditions such as obstructive sleep apnoea.
Beckett NS, Peters R, Fletcher AE et al; HYVET Study Group (2008) Treatment of hypertension in patients 80 years of age or older. N Engl J Med 358(18): 188798 Clement DL, De Buyzere ML, De Bacquer DA et al; Office versus Ambulatory Pressure Study Investigators (2003) Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med 348(24): 240715 Jamerson K, Weber MA, Bakris GL et al; ACCOMPLISH Trial Investigators (2008) Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 359(23): 241728 Hodgkinson J, Mant J, Martin U et al (2011) Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: Systematic review. BMJ 342: d3621 Langer RD, Criqui MH, Barrett-Connor EL et al (1993) Blood pressure change and survival after age 75. Hypertension 22(4): 5519 NHS Employers, British Medical Association (2012) Quality and Outcomes Framework for 2012/13. Guidance for PCOs and practices. www.nhsemployers.org/Aboutus/Publications/ Documents/QOF_2012-13.pdf (accessed 11 January 2013) National Institute for Health and Clinical Excellence (2009) NICE clinical guideline 76. Medicines adherence: Involving patients in decisions about prescribed medicines and supporting adherence. www.nice.org.uk/nicemedia/live/11766/43042/43042.pdf (accessed 11 January 2013)

Key Points
The diagnosis of hypertension should be based on the daytime average blood pressure (BP) from an ambulatory BP monitor using a BP threshold of 135/85 mmHg Cardiovascular (CV) risk assessment should be undertaken for all patients with hypertension, unless there is evidence that they are already at high risk (e.g. the presence of CV disease, diabetes, renal disease, or other target organ damage) Patients with stage 1 hypertension and low or moderate CV risk (<20% over 10 years) should be managed with lifestyle interventions to control their BP Patients with stage 2 hypertension and those with stage 1 hypertension at high CV risk (20% over 10 years) or with evidence of target organ damage should be offered drug therapy and lifestyle interventions to control their BP Drug choice should be guided by patient age and ethnicity in line with the NICE treatment algorithm, but may need to be tailored to the specific patient based on efficacy and tolerability Patients should be treated to achieve a clinic BP target of <140/90 mmHg, except those older than 80 years, in whom a clinic BP target of <150/90 mmHg is recommended Non-adherence is a key issue in managing hypertension and prescribers should utilise strategies to address both intentional and non-intentional non-adherence

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