|NICE Clinical Guideline 127 on the clinical management of primary hypertension in adults has been awarded the NHS Evidence Accreditation Mark. This Mark identifies the most robustly produced guidance available. See evidence.nhs.uk/accreditation for further details.|
Hypertension affects nearly 25% of the UK adult population and over 50% of people aged over 65 years, and is a major risk factor for stroke and myocardial infarction.1 Worldwide, high blood pressure is responsible for approximately 13% of total deaths.2 It is known that risk rises in a linear fashion and the risk of a cardiovascular event doubles for each 20 mmHg rise in systolic blood pressure and 10 mmHg rise in diastolic blood pressure. It is estimated that 12% of the primary care workload is involved in the management of hypertension.3
The first guideline from NICE on hypertension was Clinical Guideline (CG) 18,4 published in 2004. Although updates are normally undertaken every 5 years, there was in this case a partial update only 2 years later, in the form of CG34.5 This update was carried out in collaboration with the British Hypertension Society (BHS). The reason for this early update was the publication of meta-analyses and trials such as ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), which questioned the effectiveness of beta blockers in treating essential hypertension.6–8 The 2006 update introduced the ACD treatment algorithm, which was well received and popular in primary care.
The new update, NICE CG127, was published in August 2011 and is a return to the normal practice of 5-yearly updates.3,9 This work was once again developed in collaboration with the BHS. Guideline Development Groups (GDGs) working on NICE updates are restricted to looking at new evidence released after publication of the guideline and they must follow the predefined scope. Most of the new data on hypertension related to the measurement of blood pressure outside the surgery. One particular trial—HYVET (Hypertension in the Very Elderly Trial)—was published in 2008,10 and led to the GDG reviewing the effectiveness of treatment in people aged over 80 years.
Key changes in the updated 2011 NICE guideline include:3,9
- using ambulatory blood pressure monitoring (ABPM) for the initial diagnosis of hypertension in all patients
- diuretics becoming third- and fourth-line treatment in the ACD algorithm
- a specific recommendation on offering blood-pressure treatment to the very elderly.
These three key changes are discussed below.
The NICE care pathway on hypertension is shown in Figure 1. The use of ABPM in the diagnosis of hypertension is recommended if the clinical blood pressure measurement (CBPM) is greater than ?140/90 mmHg. The CBPM should be determined by taking at least three measurements, 1 minute apart, with the patient rested and relaxed. The lowest value from the second or third measurement is usually the most reliable.3,9 Unlike previous practice where the patient would return for three or four consultations, the recommendation is now to go straight to ABPM, unless this is not tolerated or not available, in which case, home blood-pressure monitoring (HBPM) should be used.
The above recommendation on ABPM is based on recent evidence11 and a detailed health-economics assessment, which was undertaken by NICE health economists together with a team from the University of Birmingham, and was published simultaneously (online) in The Lancet.12 The members of the GDG were surprised that ABPM came out on top, but the cost savings are impressive and achieved by the need for fewer consultations as well as the elimination of unnecessary treatment of patients. The guideline suggests a minimum of 14 readings taken during the day;3,9 night-time measurements are unnecessary. The need to use ABPM may become a requirement of the quality and outcomes framework in years to come.
For HBPM, it is recommended that the patient takes two resting blood pressures, 1 minute apart, twice daily. They should do this for 4 to 7 consecutive days and ignore the readings taken on the first day. This regimen is similar to the instructions used in most of the evidence-based studies.13–16 In essence, the average reading will be more accurate with a higher number of readings. The general feeling was that when further trial data become available, HBPM will eventually be shown to be similar in efficacy to ABPM.
We know that out-of-surgery measurements do not equate to ones taken in the practice and previously it was recommended to add either 10/5 or 5/5 to the ambulatory or home readings to correct for this. In the updated NICE guideline, specific diagnostic thresholds of 135/85 mmHg for stage 1 hypertension and 150/95 mmHg for stage 2 hypertension are recommended for both ABPM and HBPM (see Box 1). If a patient aged below 80 years has stage 1 hypertension with target organ damage or stage 2 hypertension at any age, drug treatment should be initiated immediately.9
Figure 1: Care pathway for hypertension3,9
The ‘ACD’ algorithm from the 2006 guideline was very popular as indicated by straw polls at meetings, and has now been revised (see Figure 2). The first-line options are as follows: for people aged below 55 years—‘A’ angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) should be used. This change in the guidance from using ARBs when ACE inhibitors are not tolerated was made as ARBs are now available as generics. For those over 55 years or who are black and of African or Carribean origin—‘C’ calcium-channel blockers are recommended.3,9
The major change in the first-line options was the preference to use calcium-channel blockers and the relegation of diuretics, which are to be used only if heart failure is imminent or present. This decision was based on evidence that calcium-channel blockers provide faster control of blood pressure and that this benefit persists through prolonged treatment.17
The use of ‘A’ plus ‘C’ is now recommended at step two. Step three is as before: ‘A’ plus ‘C’ plus ‘D’, except ‘D’ is now a thiazide-like diuretic, such as chlortalidone or indapamide.3,9 The decision to specify thiazide-like diuretics is based on the fact that most end-point trials used these drugs. The Medical Research Council trial used bendroflumethiazide and is responsible for the widespread use of this drug in UK practice.18 The dose of bendroflumethiazide used in this trial was 10 mg and therefore not the dosage that we all use commonly. The NICE guidance suggests using thiazide-like drugs for new prescriptions only, and not to switch patients who are already on a thiazide and are well controlled.3,9
A major change in the treatment algorithm is the recommendation that resistant hypertension is addressed with a fourth-line therapy. In particular, the aldosterone antagonist, spironolactone, should be considered for patients in whom the blood potassium level is lower than 4.5 mmol/l. In patients with a potassium level higher than 4.5 mmol/l, higher doses of thiazide-like diuretics should be considered.3,9 The evidence base for treatment of resistant hypertension is weak and available data, mainly supports the use of spironolactone.19,20
|Box 1: Diagnostic thresholds for hypertension3,9|
written by Dr David Jenner, NHS Alliance GMS contract/PBC Lead
Stage 1 hypertension:
Stage 2 hypertension:
BP=blood pressure; ABPM=ambulatory blood pressure monitoring; HBPM=home blood pressure monitoring
National Institute for Health and Care Excellence (NICE) (2011) CG127. Hypertension: clinical management of primary hypertension in adults (update). London: NICE. Reproduced with permission. Available from www.nice.org.uk/guidance/CG127
Treating hypertension in the very elderly
Prior to publication of the HYVET results in 2008, it was believed that treating hypertension in people aged over 80 years was as likely to cause harm as well as provide benefit. Previous sub-group meta-analysis suggested that although stroke incidence would fall, overall mortality would be increased.21 Many people believed this was due to a heightened susceptibility to falls. The only randomised controlled trial to be performed in this age group is HYVET, which showed that treatment of hypertension provides benefits in terms of reductions in the number of strokes, all cardiovascular end points, all-cause mortality, and a very significant reduction in new onset of heart failure.10 As a result of these trial data, the updated guideline recommends treatment in people aged over 80 years, but with a higher target.3,9
The NICE guideline states specifically that healthcare professionals should look for evidence of postural hypotension and use the standing blood-pressure measurement if this diagnosis is made.3,9 Postural hypotension is much more likely in the very elderly. It should be noted that the participants in HYVET were specifically healthy, with dementia and residential care patients excluded.10
Figure 2: Summary of antihypertensive drug treatment3,9
Monitoring and treatment targets
It was considered impractical to use out-of-surgery methods to monitor blood pressure and the evidence base is not sufficient to support a change in current practice. The exception to this advice is the use of ABPM or HBPM for people who have the ‘white-coat effect’.
Therefore the response to antihypertensive treatment should be monitored with CBPM; target levels are as follows:3,9
- <140/90 mmHg (or <135/85 mmHg if using ABPM or HBPM) for people aged under 80 years
- <150/90 mmHg (as used in HYVET) (or <145/85 mmHg if using ABPM or HBPM) for people aged over 80 years.
The greatest challenge will be the introduction of ABPM, which is estimated by the device manufacturers to be available in less than 10% of primary care practices. Cost is one issue although with the greater use of ABPM it is predicted that the price of devices will come down and equipment manufacturers are likely to develop machines specifically to comply with this recommendation. Training of nursing staff to use the equipment will also be required. A greater challenge may perhaps be the changing of the habit of a lifetime, namely bringing patients back for repeated measurements.
Many healthcare professionals will treat the use of spironolactone with caution. It is important to carry out regular electrolyte checks with aldosterone antagonists, such as spironolactone, and it is also worth warning patients that if they have a dehydrating illness such as gastroenteritis, they should temporarily stop taking the drug.
NICE has developed the following tools to support implementation of Clinical Guideline 127 on Hypertension: clinical management of primary hypertension in adults (update). The tools are now available to download from the NICE website: www.nice.org.uk/CG127
Baseline assessment tool
Clinical audit tools
Clinical case scenarios
Electronic audit tool
ABPM implementation podcast
As is true for all NICE guidelines, the GDG was limited to answering specific questions from the scope and any topics outside this area were not addressed. The updated guideline on hypertension does not cover treatment of patients with diabetes, pregnant women, or children as these topics are the subjects of other NICE guidelines; additionally, complicated, acute or secondary hypertension was not considered.
The NICE guideline on hypertension in pregnancy (CG107)22 was based on very little evidence as trials in pregnancy are fraught with difficulty. The evidence for adult hypertension is more readily available, but there are areas of weak data. In particular, there are very few studies for third- and fourth-line therapy. Nearly all end-point evidence is based on people aged over 50 years; for those below 50 years, we rely on surrogate marker evidence (i.e. lowering of blood pressure and the assumption that this reduces morbidity and mortality). There was no good evidence for improved outcomes with treatment targets below 140/90 mmHg, and therefore the guideline does not recommend a change in these targets.
The NICE guideline on hypertension supports faster and more accurate diagnosis using out-of-surgery measurements, preferably using ABPM. This is the key challenge for primary care in terms of implementing this recommendation. People who are very elderly should be treated, but to more conservative targets based on evidence from HYVET in which patients were generally healthy. The use of diuretics is now mainly as third- and fourth-line options, but greater use of thiazide-like diuretics is advocated. The use of spironolactone or higher doses of thiazide-like diuretics is suggested as a primary care response to resistant hypertension before referral to secondary care is considered.
- Department of Health. Health survey for England, 2009. www.ic.nhs.uk/ webfiles/publications/003_Health_Lifestyles/hse09report/HSE_09__Volume1.pdf
- World Health Organization. The World Health report 2002; reducing risks, promoting healthy life. Geneva: WHO, 2002.
- National Clinical Guideline Centre. Hypertension: the clinical management of primary hypertension in adults. Clinical Guideline 127. London: NCGC, 2011. Available at: publications.nice.org.uk/hypertension-cg127
- National Institute for Health and Care Excellence. Hypertension (persistently high blood pressure) in adults. Clinical Guideline 18. London: NICE, 2004.
- National Institute for Health and Care Excellence. Hypertension: management in adults in primary care: pharmacological update. London: NICE, 2006.
- Dahlof B, Sever P, Poulter N et al; ASCOT Investigators. 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 2005; 366 (9489): 895–906.
- Carlberg B, Samuelsson O, Lindholm L. Atenolol in hypertension: is it a wise choice? Lancet 2004; 364: 1684–1689.
- Lindholm L, Carlberg B, Samuelsson O. Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366 (9496): 1545–1553.
- National Institute for Health and Care Excellence. Hypertension: clinical management of primary hypertension in adults (update). Clinical Guideline 127. London: NICE, 2011. Available at: www.nice.org.uk/guidance/CG127
- Beckett N, Peters R, Fletcher A et al. HYVET study group. treatment of hypertension in patients 80 years of age or older. NEJM 2008; 358 (18): 1887–1898.
- Fagard R, Cornelissen V. Incidence of cardiovascular events in white-coat, masked and sustained hypertension versus true normotension: a meta-analysis. J Hypertens 2007; 25 (11): 2193–2198.
- Lovibond K, Jowett S, Barton P et al. Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modeling study. Lancet 2011; 378 (9798): 1219–1230.
- Bobrie G, Chatellier G, Genes N et al. Cardiovascular prognosis of "masked hypertension” detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA 2004; 291 (11): 1342–1349.
- Fagard R, Van Den Broeke C, De Cort P. Prognostic significance of blood pressure measured in the office, at home and during ambulatory monitoring in older patients in general practice. J Hum Hypertens 2005; 19 (10): 801–807.
- Sega R, Facchetti R, Bombelli M et al. Prognostic value of ambulatory and home blood pressures compared with office blood pressure in the general population: follow-up results from the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. Circulation 2005; 111 (14): 1777–1783.
- Stergiou G, Baibas N, Kalogeropoulos P. Cardiovascular risk prediction based on home blood pressure measurement: the Didima study. J Hypertens 2007; 25 (8): 1590–1596.
- Julius S, Kjeldsen S, Weber M et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363 (9426): 2022–2031.
- MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party. Br Med J 1985; 291 (6488): 97–104.
- Chapman N, Dobson J, Wilson S et al; Anglo-Scandinavian Cardiac Outcomes Trial Investigators. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49 (4): 839–845.
- de Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension 2010; 55 (1): 147–152.
- Gueyffier F, Bulpitt C, Boissel J et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDANA Group. Lancet 1999; 353 (9155): 793–796.
- National Institute for Health and Care Excellence. Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. Clinical Guideline 107. London: NICE, 2010. Available at: www.nice.org.uk/guidance/CG107 G