New evidence-based recommendations from NICE will help GPs treat essential hypertension appropriately, says Dr Alan Begg


   

The National Institute for Clinical Excellence recently published Clinical Guideline 18. Hypertension – management of hypertension in adults in primary care.1 The guideline is aimed at GPs, practice nurses and other primary healthcare professionals who have direct contact with patients.

The guideline provides up-to-date evidence-based recommendations for the appropriate management of persistently raised blood pressure when there is no primary cause (Figure 1, below). The grading scheme is explained in Figure 2 (below).

Figure 1: Management flowchart for raised blood pressure 1,2
Reproduced with the kind permission of the National Institute for Clinincal Excellence
Figure 2: Grading scheme used in the NICE guideline 1
Reproduced with the kind permission of the National Institute for Clinincal Excellence

The key recommendations on lifestyle change, pharmacological intervention and drug use based on the level of evidence receive high grades of recommendation. In contrast, however, the recommendation against the use of automated devices in primary care is graded only C, while the processes of measuring and monitoring blood pressure tend to have the least evidence and are graded lower still.

The guideline addresses the relative benefits and potential risks of long term treatment as well as its cost. Guidance is also given as to when it may be possible to reduce or stop drug therapy. The guideline does not however address:

  • Screening for or prevention of hypertension
  • Approach to high normal blood pressure
  • Hypertension in pregnancy
  • Specialist management of secondary hypertension.

Nor does it make any specific recommendations for the control of hypertension in patients with diabetes mellitus.

The guideline does not consider the hospital setting, but it does give criteria as to when referral to secondary care is appropriate. The key points are summarised in Box 1 (below).

Taking blood pressure

The guideline rightly emphasises that healthcare professionals who take blood pressure should receive initial training and prove competency through periodic review of their performance. They also have a responsibility to ensure that they are using both appropriately calibrated equipment and a correct technique.

Lifestyle change

Appropriate lifestyle change is important for all patients with raised blood pressure. A healthy diet and regular exercise can reduce blood pressure but education about lifestyle on its own is unlikely to be effective.

The recommended lifestyle advice is broadly in line with previous guidelines:

  • Follow a healthy diet, low-calorie if overweight
  • Undertake aerobic exercise for 30-60 minutes, 3-5 times per week
  • Limit alcohol intake to less than 21 units per week for men and 14 units per week for women
  • Reduce excessive consumption of coffee and caffeine rich products
  • Reduce dietary sodium to less than 6g per day by reducing table salt or replacing it with reduced sodium salt.

Patients should also be informed about local groups that encourage healthy lifestyle change.

Although relaxation therapies can reduce blood pressure it is not recommended that this should be an intervention carried out by primary care teams.

Stopping smoking will not decrease blood pressure 5 but the resulting reduction in cardiovascular risk is more important.

The current evidence does not show that calcium, magnesium or potassium supplements produce sustained reductions in blood pressure.

Drug therapy

An outline of the main classes of drugs used in the management of hypertension is given in Table 1 (below). The guideline recommends that drug therapy should normally begin with a low-dose thiazide-type diuretic. A beta-blocker should be the second line ‘add-in’ unless the patient is at increased risk of new onset diabetes, when an ACE inhibitor should be used. Third-line choice is a dihydropyridine calcium-channel blocker (Figure 1).

Table 1: Outline of drugs used for essentail hypertension 2
Reproduced with the kind permission of the National Institute for Clinincal Excellence

Underpinning these recommendations is a systematic review of the outcome of major hypertension trials involving 200 or more patients. The main morbidity and mortality outcomes are summarised in Table 2 (below).

Table 2: Systematic review of outcomes in hypertension trials
Drug group Outcomes
Low-dose thiazide-type diuretics Statistically significant reductions in mortality of 9%, myocardial infarction of 22% and stroke of 31%
Beta-blocker Statistically significant reduction in risk of stroke of 19% and non-significant reductions in risk of death of 6% and of myocardial infarction of 8%
ACE-inhibitors The PROGRESS3 trial met the review inclusion criteria but did not show an overall reduction in mortality. There were statistically significant relative reductions in coronary events of 24% and stroke of 27%
Angiotensin II receptor blockers One trial (SCOPE)4 showed a borderline statistically significant reduction in stroke primarily due to reduced non fatal stroke
Calcium-channel blockers One trial of isolated systolic hypertension showed a possible reduction in coronary events and a statistically significant reduction in stroke
Alpha blockers No placebo controlled trials were identified that met the review criteria

The recommendations contrast with those of the recent guideline from the British Hypertension Society (BHS),6 which uses the AB/CD algorithm for initial therapy and subsequent logical combinations7 although randomised controlled trials have yet to validate this algorithm.

The combinations recommended by the BHS are, however, similar to those used in hypertension randomised controlled trials and take into account how the different drugs work. Younger caucasian hypertensive patients tend to have higher levels of renin and angiotensin II, and the evidence suggests that starting these patients on a drug such as an ACE inhibitor, angiotensin II receptor blocker or beta-blocker, which blocks the renin-angiotensin system, will give optimal blood pressure lowering. However these drugs may be less effective in older patients or those of African origin, who are likely to have low renin hypertension, so starting with a diuretic or calcium-channel blocker may be more appropriate for this group.

The transition from the younger to older age group occurs between 50 and 60 years, and is taken as 55 years for practical purposes. Renin blockade in younger patients is reflected in the NICE recommendation that patients aged under 55 with moderately raised blood pressure should be considered for commencement on a beta-blocker if they are likely to be managed on only one drug.

New-onset diabetes

A recent review of the diabetogenic effect of anti-hypertensive treatment identified five prospective randomised hypertension trials with differing rates of new onset diabetes in patients on various antihypertension therapies.8

The NICE group also considered two additional trials. In the CAPPP 9 study there was a statistically higher rate of new onset diabetes in patients randomised to diuretics and beta-blockers, and in the LIFE study 10,11 there was a 25% lower rate of new-onset diabetes in the angiotensin II receptor blocker group compared with those on a betablocker.

At present it is not possible to determine whether the increase in new onset diabetes is attributable to the combination of a thiazide-type diuretic and beta-blocker or the individual drugs. However, the unanimous consensus of the NICE guideline group was that it would be sensible to restrict the use of a combination of thiazide-type diuretics and beta-blockers when starting treatment in patients at increased risk of diabetes.

New trial evidence

The VALUE trial,12 which recently reported, may influence the debate about initial choice of therapy, drug combinations and the risk of new onset diabetes. This trial compared an angiotensin II receptor blocker with a calcium-channel blocker. Hydrochlorothiazide was the add-in therapy in both groups.

The initial faster reduction in blood pressure with the calcium-channel blocker based regimen may account for the lower incidence of myocardial infarction and stroke in this group, indicating that the degree of blood pressure lowering is an important factor. However, in the group treated with an angiotensin II receptor blocker there was a 23% reduction in the development of new onset diabetes.

Other management points

  • Treat patients with isolated systolic hypertension similarly to other patients with raised blood pressure.
  • Offer patients over 80 years of age the same treatment as younger patients, taking into account comorbidities and current burden of drug use.
  • Improve adherence by using, if possible, a once daily blood pressure lowering regimen.
  • Prescribe non-proprietary drugs where appropriate.

Economic issues

The benefits of lowering raised blood pressure to reduce cardiovascular events are not in doubt. Economic modelling carried out as part of the guideline development process produced an average figure of about £2250 per quality adjusted life-year (QALY) gained which compares favourably with the current NICE threshold for new technologies of £30 000 per QALY.

The guideline concludes that beginning drug treatment with either a non-proprietary thiazide diuretic or a beta-blocker minimises cost, and stepped care as outlined using the commonly used agents is estimated to be cost effective.

Guideline implementation

Development of the NICE guideline has involved a comprehensive appraisal of an extensive evidence base, but apart from the advice about choice of initial drug therapy that conflicts with the BHS guidelines, its recommendations are unlikely to lead to an immediate change in clinical practice.

  • The cut-off point for classifying hypertension is >140/90 mmHg as opposed to >=140/90 mmHg in the BHS guidelines.
  • The suggested target on treatment is 140/90 mmHg, compared with <140/85 mmHg (for patients without diabetes) in the BHS guidelines and the minimum audit standard of 150/90 mmHg or less in the new General Medical Services contract.13
  • Automated ambulatory blood pressure or home monitoring devices are not recommended for use in primary care as their value is not clearly established.
  • Annual review is recommended compared with a maximum interval of 9 months between reviews under the new GMS contract.
  • The BHS guidelines recommend that those with high normal blood pressure (systolic blood pressure 130-139 mmHg, diastolic blood pressure 85-89 mmHg) should be checked annually, but NICE recommends that all those whose blood pressure is not above the threshold of 140/90 mmHg are checked five-yearly.

Ongoing audit of hypertensive patients will in time determine which management approach will prevail in clinical practice.

NICE Clinical Guideline 18. Hypertension – management of hypertension in adults in primary care, the full guideline from the North of England Hypertension Guidelines Development Group, a quick reference guide, a poster, and information for the public can all be downloaded from the NICE website, www.nice.org.uk.

References

  1. National Institute for Clinical Excellence. Clinical Guideline 18. Hypertension – management of hypertension in adults in primary care. NICE, London:August 2004.
  2. North of England Hypertension Guidelines Development Group, Evidence-based Clinical Practice Guideline.Essential hypertension:managing adult patients in primary care. NICE,London:August 2004.
  3. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressurelowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358: 1033-41.
  4. Lithell H, Hansson L, Skoog I et al; SCOPE Study Group.The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21(5): 875-86.
  5. Omvik P. How smoking affects blood pressure. Blood Press 1996; 5(2): 71-7.
  6. Williams B, Poulter NR, Brown MJ et al; British Hypertension Society. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004- BHS IV. J Hum Hypertens 2004; 18(3): 139-85.
  7. Brown MJ, Cruickshank JK, Dominiczak AF et al; Executive Committee, British Hypertension Society. Better blood pressure control: how to combine drugs. J Hum Hypertens 2003;17(2):81-6.
  8. Dusing R, Lehnert H. Diabetogenic effect of antihypertensive treatment: primum nil nocere. Nephrol Dial Transplant 2004; 19(3): 531-4.
  9. Hansson L, Lindholm LH, Niskanen L et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.Lancet 1999; 353; 611-6.
  10. Lindholm LH, Ibsen H, Dahlof B et al; LIFE Study Group.Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 1004-10.
  11. Dahlof B, Devereux RB, Kjeldsen SE et al; LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995-1003.
  12. Julius S, Kjeldsen SE, Weber M, et al; VALUE trial group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022-31.
  13. Investing in General Practice: The New General Medical Services Contract. www.bma.org.uk

Guidelines in Practice, October 2004, Volume 7(10)
© 2004 MGP Ltd
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