Management of hypertension: summary of NICE guidance
Cite this as: BMJ 2011;343:d4891
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In reponse to Kate Harding.
Choice of Antihypertensive Drug for Use in Pregnancy:
The Food and Drug Administration reviews human and animal data to assign letter grades corresponding with risk of fetal exposure in pregnancy. Most antihypertensive agents used in pregnancy are designated as “category C,” which states that human studies are lacking, animal studies are either positive for fetal risk or are lacking, and the drug should be given only if potential benefits justify potential risks to the fetus.1
Only small number of currently available drugs have been evaluated in pregnant women adequately and many others are contraindicated.
1. Lindheimer MD, Barron WM. Medical Disorders in Pregnancy, 3rd ed. St. Louis: Mosby; 2000.
Competing interests: None declared
Indian Council of Medical Research, Ansari Nagar, New Delhi-110029
I am grateful to Anas El Turabi and Payne for their intervention, highlighting the poor quality of evidence available to make prescribing decisions for British Black (African-Caribbean origin) people. They are correct in their assertion that we do not know with certainty if this is the right baseline data for this group, many of whom (as highlighted in recent TV and media coverage) may in fact belong to the emergent 'mixed' origin population of the UK, and be genetically significantly different from the Black American population referred to. However, as the 'BiDil' controversy in the USA made it clear, at least for a significant proportion, renin functions and genetic predispositions may mean that 'generic' advice is not totally appropriate either. In other clinical areas, we also know that people of South Asian or Mediterranean origin may have varying sensitivities to certain drugs. At least Krause et al have highlighted the possibility that Black patients might need specific consideration. Williams' response on behalf of the team also underlines the need for us to seek more and better research evidence on the efficacy of treatments in different ethnic groups - and indeed, age groups. It is not so long since it had to be argued that we needed to have hard evidence of gender differences in susceptibility to side effects.
This small controversy at least helps to highlight the case that the UK Centre for Evidence in Ethnicity Health & Diversity (and until recently, the NHS Evidence 'specialist collection' on ethnicity and health') has been making for the past 15 years! Can we please ask all future therapeutic trials to ensure a satisfactory inclusion of minority ethnic groups - and where appropriate, age groups, to provide safer and more effective recommendations on the use of treatments?
Competing interests: Dr Johnson directs a programme of research into the delivery of health care services to ethnically diverse communities, and health inequalities and has an interest in there being more and better research in this area. MSRC is the home of CEEHD / NHS E&H.
Mary Seacole Research Centre, De Montfort University
We thank Dr. Taylor for his comments on the recent NICE guidance on the management of primary hypertension in adults [1,2]. The guideline recommends that when a diagnosis of hypertension is suspected on the basis of a clinic blood pressure (BP) reading, the diagnosis should be confirmed by using ambulatory blood pressure monitoring (ABPM). The guideline development group (GDG) considered all data on the prognostic value of ABPM compared to conventional clinic blood pressure monitoring (CBPM) and home blood pressure monitoring (HBPM). This systematic review found ABPM was the best predictor of clinical outcomes, i.e. major cardiovascular events and mortality. For this reason the decision to use ABPM as the reference standard for diagnosis in the subsequent analyses was considered appropriate by the GDG. The systematic review and meta analysis of diagnostic studies directly comparing the sensitivity and specificity of clinic and home BP measurement strategies to a reference standard of ABPM for diagnosis concluded that neither "had sufficient sensitivity or specificity to be recommended as a single diagnostic test" and "might result in substantial over-diagnosis" . The GDG had the same concerns as Dr. Taylor about whether it would be cost-effective to routinely deploy ABPM to confirm the diagnosis of hypertension. Thus, the GDG requested a detailed cost-effectiveness analysis which found ABPM to be the most cost- effective diagnostic strategy, and indeed cost saving over the medium term . This conclusion remained robust across a wide range of sensitivity analyses modelling a variety of extreme scenarios and when using a probabilistic analysis which takes account of the uncertainty around model inputs. We recognise that implementing this major change in practice will be a challenge but the evidence suggests that it is the most accurate and cost-effective way to ensure that those with hypertension are accurately identified and treated.
In response to Dr. Cruickshank's comments about the exclusion of beta -blockers as a preferred treatment of hypertension, unless there is a compelling indication for beta-blockers beyond the need to lower blood pressure, this decision was taken in the NICE hypertension guideline update in 2006 . Briefly, the analysis of data showed that for the treatment of primary hypertension, beta-blockers were effective at reducing the risk of major cardiovascular events but when compared to the currently recommended treatments, they were significantly less effective at reducing the risk of stroke and no more effective at preventing the risk of myocardial infarction . In the up-dated cost-effectiveness analysis of the treatment of primary hypertension in the current guidance, beta-blockers were the least cost-effective treatment option . Furthermore, similar conclusions have been reached in other independent analysis [6,7]. Dr. Cruickshank's assertion that the later generation of more selective beta blockers may be more effective at reducing cardiovascular risk than older generation beta blockers in people with hypertension, cannot be substantiated by reference to evidence from clinical outcome trials with these drugs in people with hypertension.
Drs. El Turabi and Payne raise important questions about the paucity of data relating to the efficacy of different classes of BP-lowering drugs in various ethnic groups, including people of Black African and Caribbean origin. In particular, they note a lack of data for younger people, i.e. under the age of 55 years. This latter point is addressed by the guideline which recommends the need for further research regarding the treatment of hypertension in all younger people. With regard to treatment outcomes, the main available data comes from the ALLHAT study, which we acknowledge does not specifically deal with treatment in younger people. However, it does show that ACE-inhibition was significantly less effective at reducing BP and the risk of stroke in Black Americans when compared to other treatments, i.e. CCB or thiazide-type diuretic. It also showed a higher incidence of angioedema associated with ACE-inhibition treatment, (albeit low rates), in the Black American cohort when compared to the rest of the study population. The recommendations with regard to people of Black African or Caribbean descent in the current guidance are largely unchanged from the recommendations in 2006, apart from the steer towards the preferred use of CCB rather than thiazide-type diuretic as initial therapy. We wholeheartedly agree that further data is needed in different ethnic groups from future trials, especially for younger people but believe that the current recommendations reflect the best available evidence to date.
Bryan Williams MD
On behalf of the Guideline Development Group.
1. National Institute for Health and Clinical Excellence. Hypertension: clinical management of primary hypertension in adults (update). (Clinical guideline 127.) 2011. http://guidance.nice.org.uk/CG127.
2. Krause T, Lovibond K, Caulfield M, McCormack T, Williams B. on behalf of the Guideline Development Group. Management of hypertension: summary of NICE guidance. BMJ 2011; 343: d4891 [Full text]
3. Hodgkinson J, Mant J, Martin U, Guo B, Hobbs FDR, Deeks J, Heneghan C, Roberts N, McManus RJ. Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review, BMJ 2011; 342:d3621
4. Lovibond K, Jowett S, Barton P, Caulfield M, Heneghan C, Hobbs R, Hodgkinson J, Mant J, Martin, U., Williams B, Wonderling D, McManus R, 2011. Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study. The Lancet - 24 August 2011 DOI: 10.1016/S0140-6736(11)61184-7
5. National Collaborating Centre for Chronic Conditions. Hypertension: management in adults in primary care: pharmacological update. (Pharmacological update of CG18.) Royal College of Physicians, 2006.
6. Wiysonge C, Bradley H, Myose B, et al. Beta-blockers for hypertension. Cochrane Database Syst Rev 2007; 1:CD002003.
7. Bangalore S, Messerli FH, Kostis JB, Pepine CJ. Cardiovascular protection using beta-blockers: a critical review of the evidence. J Am Coll Cardiol 2007;50: 563-72.
8. Leenen FH, Nwachuku CE, Black HR, Cushman WC, Davis BR, Simpson LM, Alderman MH, Atlas SA, Basile JN, Cuyjet AB, Dart R, Felicetta JV, Grimm RH, Haywood LJ, Jafri SZ, Proschan MA, Thadani U, Whelton PK, Wright JT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid- lowering treatment to prevent heart attack trial. Hypertension. 2006; 48(3):374-384.
Competing interests: None declared
Department of Cardiovascular Sciences, University of Leicester
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We agree with Kate Harding and Andrew Shennan that when considering the treatment of hypertension, it is important to emphasise that special consideration should be given to prescribing of antihypertensive therapy in women of child bearing potential.
Specific recommendations with this aim were included in the recently published full NICE guidance on the management of primary hypertension in adults(NICE clinical guideline 127) and the accompanying quick reference guide. These state; "Offer antihypertensive drug treatment to women of child-bearing potential in line with the recommendations on Management of pregnancy with chronic hypertension and Breastfeeding in 'Hypertension in pregnancy' (NICE clinical guideline 107). The guidance goes on to recommend; "Tell women who take angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) that there is an increased risk of congenital abnormalities if these drugs are taken during pregnancy and to discuss other antihypertensive treatment with the healthcare professional responsible for managing their hypertension, if they are planning pregnancy." Followed by the recommendation to "Stop antihypertensive treatment in women taking ACE inhibitors or ARBs if they become pregnant (preferably within 2 working days of notification of pregnancy) and offer alternatives" and to "to discuss other antihypertensive treatment with the healthcare professional responsible for managing their hypertension, if they are planning pregnancy".
These important sections were omitted in the brief version of the NICE hypertension guideline summary published in the BMJ and we thank the authors for drawing this to our attention. Fortunately, this important guidance is included in all of the NICE guideline outputs.
Competing interests: As declared in the original BMJ article on NICE guidance
NICE Hypertension Guideline Development Group
The new edition of the NICE guidelines of Hypertension[1, 2] recommends for treatment of resistant hypertension at step 4, either the use of a higher dose of thiazide-like diuretic, or the addition of the aldosterone antagonist spironolactone. Both strategies work reducing the intravascular volume expansion that is almost always present in resistant hypertension, by forcing sodium and water renal excretion.
We miss in this guide and others, more concern for the other mechanism that prevents volume overload in resistant hypertension which is the reduction of salt ingestion and consequently water retention.
Unfortunately, the clinical effect on blood pressure of sodium restriction in patients with resistant hypertension has insufficiently been studied. Only a recent 4-week randomized cross-over study which included 12 patients suggests, that patients with resistant hypertension are exquisitely salt sensitive. The blood pressure reduction achieved during the low-salt ingestion period, as high as 22.7/9.1 mm Hg, was estimated as being equivalent to adding 2 antihypertensive medications.
Many hypertension clinics and primary-care physicians use 24-hours urinary sodium measurements as a method to detect a poor adherence with salt dietary restriction. Our experience is that a value of sodium excretion >120 mmol/24-hour allow clinicians to convince patients that they are not doing sufficient efforts with sodium intake restriction. Many patients change their attitude, improve their accomplishment with our advice and finally reach the blood pressure objectives
While more evidence be available, we believe that to control resistant hypertension and to diminish iatrogenic risk, it is appropriate, before or during pharmacologic modifications at step 4, not only to attempt dietary modification again, but also to provide assurance that salt restriction is effective by performing 24-hour urinary sodium measurements.
 National Institute for Health and Clinical Excellence. Hypertension: clinical management of primary hypertension in adults. CG127. 2011. http://guidance.nice.org.uk/CG127/Guidance/pdf/English
 Guidelines: Management of hypertension: summary of NICE guidance. Taryn Krause, Kate Lovibond, Mark Caulfield, Terry McCormack, Bryan Williams, on behalf of the Guideline Development Group. BMJ 2011;343:doi:10.1136/bmj.d4891 (Published 25 August 2011)
 Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, Pimenta E, Aban I, Oparil S, et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch Intern Med. 2008;168:1159-64. [PMID: 18541823]
 Pimenta E, Gaddam KK, Oparil S, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension. 2009;54:475-81
Competing interests: None declared
Las Aguilas Primary Care Unit, Consejeria de Sanidad. Madrid. Spain
In the summary NICE guidance on the management of hypertension (1) the advice on the more regular use of home or ambulatory blood pressure monitoring (to avoid "white-coat effect" seen in the clinic) was particularly welcome. However their guidance on the first-line treatment of hypertensives under the age of 55 years, with either an ACE inhibitor or angiotensin receptor blocker (ARB), with no mention of beta-blockade, is particularly hard to understand or accept.
There has been only one randomised, hard-endpoint comparison between ACE-inhibitors and beta-blockers and that is the UKPDS study in middle- aged, obese hypertensives with type-2 diabetes (2). After 9-10 years follow-up the trends (vs less tight control of blood pressure) in the reduction of the 7 primary endpoints (plus the important secondary endpoint of heart failure) all favoured the beta-blocker atenolol over the ACE inhibitor captopril. Clearly the atenolol-induced increase in HbA1-c over the first 4 years was of no clinical import. Significantly, after 20 years follow-up (patients discharged to primary care at 10 years), the trends noted at 10 years follow-up favouring those randomised to atenolol for the reduction of myocardial infarction, peripheral vascular disease and microvascular disease persisted, and in the case of all-cause death strengthened to a significant 23% reduction (3). So how could an ACE inhibitor be favoured over a beta-blocker? Is a brief increase in HbA1-c (plus cost implications) to be considered more important than a life- saving quality? : surely not. Besides, the tendency for non-selective and moderately selective beta-blockers to induce metabolic disturbance can be avoided by the use of a highly beta-1 selective agent e.g. bisoprolol (4). Not only does bisoprolol avoid metabolic disturbance but is also the most effective way to lower blood pressure in young-middle-aged hypertensives (5).
The apparent disappointing results of other randomised, controlled, hard-endpoint beta-blocker studies in middle-aged hypertensives i.e. MRC mild hypertension (non-selective propranolol), IPPPSH (non-selective oxprenolol) and MAPHY (moderately beta-1 selective metoprolol), was due to an important (often unrecognised) smoking-interaction (4). In those 3 studies, in the approximate 70% non-smoking population, the beta-blocker reduced the risk myocardial infarction (number 1 killer, being about 3 times more common than stroke) by about 35-50% vs placebo or diuretic (4). This benefit was totally cancelled out in the smokers due to the marked hypertensive reaction occurring with non-selective or poorly selective beta-blockers in the presence of smoking-induced increases in adrenaline (4). Again this dangerous beta-blocker/smoking/adrenaline interaction can be avoided by high beta-1 selectivity i.e. bisoprolol (4).
The recommendation of an ARB as an alternative to ACE inhibitor for the treatment of hypertensives under the age of 55 years is particularly worrying, in view of the possibility that ARBs may increase the risk of myocardial infarction (6). This concern was underlined by the results of a recent randomised, placebo-controlled study in over 4000 middle-aged type- 2 diabetics with pre-hypertension (7). The number of deaths from cardiovascular causes was higher in the ARB (olmesartan) group than in the placebo group (13 vs 3, p = 0.01), owing primarily to more cases of fatal myocardial infarction (5 vs 0) and sudden cardiac deaths (7 v 1) in the ARB group.
Is it too late for the NICE guidance group to modify their recommendations?
1 Krause T, Lovibond K, Caufield M, McCormack T, Williams B. Managment of hypertension: summary of NICE guidance. BMJ 2011;343: d 4891.
2 UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998;317:713-9.
3 Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow- up after tight control of blood pressure in type-2 diabetes. N Eng JM 2008;359:1565-76.
4 Cruickshank JM. The modern role of beta-blockers in cardiovascular medicine. Peoples Medical Publishing House, USA Shelton, Connecticut, 2011.
5 Deary AJ, Schumann AL, Marfet H, Haydock S, Foo RS-Y, Brown MJ. Double blind, placebo-controlled crossover comparison of 5 classes of antihypertensive drugs. J Hypertens 2002;20:771-7.
6 Strauss MH, Hall A. Renin-angiotensin system and cardiovascular risk. Lancet 2007;370:24-5.
7 Haller H, Sadayoshi I, Izzo JL, Januszewicz A, Katayama S, Menne J etal. Olmesartan for the delay or prevention of microalbuminuria in type- 2 diabetes. N Engl J Med 2011;364:907-17.
Competing interests: None declared
Long Melford, Suffolk
I read with interest your recent publication of the NICE guidelines for Hypertension. The guidelines are comprehensive yet it is disappointing that there is little guidance on the management of acute hypertension. Acute hypertension is rarely mentioned in current guidelines and recommendations. Current consensus is that hypertension is best left alone in an acute setting and as a consequence it is often undertreated.
I wanted to draw your attention to the recent research carried out by the STAT registry in America. This research found that the treatment of acute hypertension is in consistent and varies considerably. As a result many patients do not receive treatment in time, have variable responses in their blood pressure and often develop hypotension. Many patients started on intravenous antihypertensives subsequently needed multiple drug therapy. It took around 4 hours to reduce systolic blood pressure to below 160 mmHg with 60% experiencing a 'reelevation' of blood pressure to over 180 mm Hg. 63% developed hypotension as a consequent of antihypertensive treatment .
The STAT study also found that a third of patients with severe hypertension were readmitted to hospital within 90 days and over a quarter of these admission were for another episode of acute hypertension . A survey of patients with severe hypertension found that they were not being treated aggresively enough . Further research was carried out on the cardiovascular sequlae of acute hypertension in kidney disease . They studied outcome in patients hospitalised with acute severe hypertension. Of these patients, Chronic kidney disease sufferers were at greater risk of developing heart failure, non ST elevation myocardial infarcts. Those with acute kidney injury were also at risk of heart failure as well as cardiac arrest. The medical consequences of untreated acute hypertension has been greatly underestimated.
The emergence of clevidipine as a new and possibly safer, more effective treatment of acute hypertension should prompt us to re-examine this area of acute medicine. Clevidipine has a short duration of action and short half life allowing its use in acute settings. It also does not cause iatorgenic hypotension. Given the need to reduce severe hypertension quickly and effectively in those with target organ damage there is an impetus to develop more anti-hypertensive medications for acute hypertension with reliable and safe blood pressure reduction. At present such blood pressure reduction is unpredictable, almost unreliable with variable results and attendant unwanted effect of hypotension. NICE and other regulatory bodies need to seriously re-examine the area of hypertension treatment in an acute setting. Physicians delivering acute medical care need more guidance in this area. The evidence for clinical sequelae of acute hypertension needs to be researched. Current management of acute hypertension is inconsistent and inadequate.
Krause T, Lovibond K, Caulfield M, McCormack T, Williams B; on behalf of the Guideline Development Group. Management of hypertension: summary of NICE guidance. BMJ2011;343:d4891
Devlin JW; Dasta JF; Kleinschmidt K; Roberts RJ; Lapointe M; Varon J; Anderson FA; Wyman A; Granger CB Patterns of antihypertensive treatment in patients with acute severe hypertension from a nonneurologic cause: Studying the Treatment of Acute Hypertension (STAT) registry. Pharmacotherapy, November 2010, vol./is. 30/11(1087-96), 0277-0008;1875-9114 (2010 Nov)
Katz JN; Gore JM; Amin A; Anderson FA; Dasta JF; Ferguson JJ; Kleinschmidt K; Mayer SA; Multz AS; Peacock WF; Peterson E; Pollack C; Sung GY; Shorr A; Varon J; Wyman A; Emery LA; Granger CB Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: the Studyingthe Treatment of Acute hyperTension (STAT) registry. : American Heart Journal, October 2009, vol./is. 158/4(599-606.e1), 0002-8703;1097-6744 (2009 Oct)
Gore JM; Peterson E; Amin A; Anderson FA Jr; Dasta JF; Levy PD; O'Neil BJ; Sung GY; Varon J; Wyman A; Granger CB Predictors of 90-day readmission among patients with acute severe hypertension. The cross-sectional observational. Studying the Treatment of Acute hyperTension (STAT) study American Heart Journal, September 2010, vol./is. 160/3(521-527.e1), 0002-8703;1097-6744 (2010 Sep)
Borzecki AM; Kader B; Berlowitz DR The epidemiology and management of severe hypertension. Journal of Human Hypertension, January 2010, vol./is. 24/1(9-18), 0950-9240;1476-5527 (2010 Jan)
Szczech LA; Granger CB; Dasta JF; Amin A; Peacock WF; McCullough PA; Devlin JW; Weir MR; Katz JN; Anderson FA Jr; Wyman A; Varon J Acute kidney injury and cardiovascular outcomes in acute severe hypertension. Circulation, May 2010, vol./is. 121/20(2183-91), 0009-7322;1524-4539 (2010 May 25)
Competing interests: None declared
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I too would agree that the new NICE Hypertension guidance, despite being well-intended, is poorly evidenced and impractical for the NHS GP.
Despite the constant revisions of treatment algorithms, diuretics are still well-evidenced for outcomes. Indications for other treatment preferences offer small benefits compared to each other, which can be dealt with by looking at 'clear contraindications' versus 'pressing indications'. In practice, whichever initial drug is chosen, most hypertensives quickly end up on middling doses of many drugs !
I am not sure that loss of GP QOF income will be an issue. White- coat patients would still be declared 'hypertensive' on the usual criteria, but exempted from drug treatment and encouraged to self-manage and avoid white-coats.
Referral for ABPM seems a care pathway to hell.
In our 6000-patient list we loan out validated home BP monitors whenever the diagnosis of sustained hypertension is in doubt. This, as NICE acknowledges, has some evidence in its favour, and has several advantages over referral for ABPM :-
short-term: 1. there is no need for secondary-care involvement 2. the patient has less inconvenience 3. the patient becomes engaged and educated 4. the NHS avoids unnecessary added costs
in the longer term, the 'white-coat patients' are encouraged either to purchase their own machine, or borrow on of ours periodically - thus giving added and ongoing reassurance to both patient and doctor.
Let us hope that NICE's new role in guiding General Practitioners through QOF does not repeat such ex-cathedra impracticalities. QOF prevalencereturns testify that 20-25% of patients are hypertensive !! The GPs on the committee will need to earn their salt if they are to sustain the respect and compliance of jobbing GPs.
Competing interests: None declared
Surgery, Newport, Pembrokeshire, SA42 oTJ
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Thanks for the summary. I note that thiazide diuretics are no longer recommended as one of the first-line medications. I do not find convincing evidence from the new NICE guidelines to justify this change.
Was this just expert opinion?
Competing interests: None declared
Prince of Wales Hospital, The Chinese University of Hong Kong
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The diagnosis and management of hypertension is bread and butter General Practice. The NICE guidance is clear in many aspects but is short on the practicalities of implementation.
The accompanying editorial mentions cost saving and upfront costs. However, it does not stress that costs will be from profitable income for the individual GP. I acknowledge that there also may be cost savings in terms of appointments at diagnosis.
For my patient list of 7000 we often have two or more cases diagnosed at the same time. Therefore access to ABPM may be problematic. There is also the issue of damaged and lost machines. At present I often suggest home blood pressure monitoring and I note this is mentioned in the guidance. This also involves greater patient involvement and understanding.
I will watch the debate on this guidance with interest.
Yours etc. etc.
Competing interests: None declared
Fforestfach Medical Centre, Swansea SA5 5AA