Hypertension treatment reduces death rates and helps very elderly patients achieve target blood pressure levels, says Dr Alan Begg


The 2004 British Hypertension Society (BHS) Guidelines for the management of hypertension indicated that the benefits of blood pressure lowering in people over the age of 80 years had yet to be established. The BHS recommends that patients already being treated for hypertension who reach the age of 80 years should continue on treatment, especially if there is evidence of target organ damage or they have other significant risk factors such as diabetes. For those over 80 years of age at the time of diagnosis, treatment should be considered on the basis of the individual and the presence or absence of other co-morbidities.1

A meta-analysis published in 1999 examined all the data on participants aged ?80 years in randomised trials of antihypertensive drugs. Of the 1670 patients studied, treatment of hypertension led to a 34% reduction in the occurrence of strokes, although this benefit was restricted to non-fatal strokes, a 22% reduction in major cardiovascular events, and a 39% reduction in heart failure. Surprisingly, there was a non-significant 6% relative excess of death from all causes, so although there was a benefit for non-fatal events, the implication was that this might come at an increased risk of death.2

HYVET

Following the suggestion of possible harmful effects of treatment, especially for total mortality, the Hypertension in the Very Elderly Trial (HYVET) was seen as the one that would clarify whether those hypertensive patients aged 80 years or over would benefit from drug-lowering therapy. The HYVET trial enrolled 3845 patients aged ?80 years at 195 centres in Europe, China, Australasia, and Tunisia, who had a sustained systolic blood pressure of ?160 mmHg at entry into the trial. The therapeutic intervention was 1.5 mg of slow-release (SR) indapamide against matching placebo. The angiotensin-converting enzyme (ACE) inhibitor perindopril in a dose of 2 or 4 mg was added if necessary in order to achieve a target blood pressure of 150/80 mmHg.

After 2 years of treatment the mean blood pressure reduction was 15/6.1 mmHg lower in the active treatment group. The improved outcomes in the HYVET active treatment group were impressive (Table 1). They demonstrated a 30% reduction in the rate of fatal or non-fatal stroke, a 39% reduction in the rate of death from stroke, a 21% reduction in the rate of death from any cause, a 23% reduction in the rate of death from cardiovascular causes, and a 64% reduction in the rate of heart failure. There were also significantly fewer serious adverse events in the active treatment group in this trial, with the baseline characteristics of the two patient groups well matched in terms of previous cardiovascular events and diabetes. The results of this trial translate into a number needed to treat of 40 to prevent one death over a 2-year period.3

Table 1: HYVET trial outcomes

 
% reduction
95% CI
p value
Primary outcome
Any fatal or non-fatal stroke excluding TIA
30
-1 to 51
0.06
Secondary outcomes: rate of death and cause
 
 
 
Any cause
21
4 to 35
0.02
Cardiovascular causes
23
-1 to 40
0.06
Stroke
39
1 to 62
0.05
Heart failure
64
42 to 78
<0.001
CI=confidence interval; TIA=transient ischaemic attack

Outcomes of the trial

The HYVET study provides evidence that using indapamide SR with or without perindopril, in a dose of 2 to 4 mg, reduces the risk of death from stroke or any other cause in patients aged ?80 years.3 It also gives an indication of the target blood pressure to aim for in these patients. As almost 50% of the patients receiving treatment reached the target blood pressure of 150/80 mmHg, it would seem reasonable to aim for this level in this category of patients.

Management of older patients

When managing patients aged 80 years or older, however, other factors need to be taken into account. These include:

  • frailty of the patients
  • presence of co-morbidities
  • if he or she is housebound
  • his or her ability to comply with taking medicines
  • level of cognitive functioning.

It should be emphasised that the HYVET patients were generally healthier than those in the general population (overall lower incidence of stroke and death from any cause, and previous incidence of CVD at start of the trial was also low), so GPs should consider the need for treatment on an individual basis.

Balancing benefit and age

The benefits of treatment also need to be considered alongside the fact that as people increase in age, the risk of dying of a stroke also increases significantly, to 52% in patients aged ?85 years.4 The Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) has recently looked at 31 trials involving 190,606 patients. The BPLTTC divided patients into those under 65 years at entry to the individual trial and those aged 65 years and over, and no clear difference between age groups in the effects of lowering blood pressure were noted.5 However, in this analysis most patients fell into a very limited age range, and the paucity of data for those over 80 years was noted. Knowing that the relative risk reduction of a cardiovascular event occurs irrespective of the patient’s age is important, as the absolute risk of a cardiovascular event is higher in older people for that same relative risk reduction. With increasing age, therefore, fewer patient years of treatment are required in order to prevent one major cardiac event.

Predicting risk of CVD

At present, GPs are encouraged to select patients for antihypertensive therapy on the basis of their global cardiovascular risk.1 Current risk prediction charts are part of the risk assessment process in patients aged up to 74 years6 but do not help to predict risk in patients with pre-existing cardiovascular disease or diabetes.

This problem of how to predict risk in the elderly was highlighted in the SIGN guideline Hypertension in older people.7 They suggested using the World Health Organization–International Society of Hypertension guideline to stratify risk and quantify prognosis on the basis of the presence of risk factors, target organ damage, and other associated clinical conditions.8 Although all these factors should be taken into account when considering treatment, it does not give a directly quantifiable measurement of risk, reinforcing the advice that the decision to commence blood pressure lowering therapy should be based on an individual clinical assessment.

Does HYVET suggest a change in approach?

At present, the choice of therapy in treating hypertensive patients is based on the fact that there is a decrease in plasma renin activity with age,9 and there may also be an age-related increase in post-synaptic alpha adrenoreceptor-mediated and calcium influx-dependent vasoconstriction.10 The BPLTTC did not present any strong evidence for the selective use of specific classes of drugs according to age,5 although the drug regimen used in the HYVET study did match the present ACD management algorithm.11 This indicates that at present, there is no need for any change to our clinical approach in the choice of antihypertensive medication.

 

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