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Until recently, there was little current evidence around the management of hypertension in people aged 80 and older. This study found that the benefits from treating hypertension probably extend to this patient group too. The NICE guidance should still be applied to those aged 80 or over, but we must be mindful of the individual patient circumstances, especially co-morbidities and their existing drug regimen.
What is the background to this?
When developing NICE guidance for the management of hypertension in adults in primary care (CG18), the guideline development group found that patients over 80 years of age are poorly represented in clinical trials. Also, the effectiveness of treatment for hypertension in this group is less certain than in the general population. NICE advised that that it is reasonable to assume that older patients will receive worthwhile benefits from drug treatment, particularly in terms of reduced risk of stroke. The NICE guidance on the management of hypertension has recently been updated (CG34) but this particular recommendation has not changed..
The Hypertension in the Very Elderly Trial (HYVET) was a large (n=3,845) double-blind randomised controlled trial, which aimed to resolve uncertainty about the relative benefits and risks of antihypertensive treatment in patients aged 80 years and older.
What does this study claim?
The HYVET study found that, at two years, antihypertensive treatment with indapamide SR 1.5mg with/without perindopril 2–4mg daily significantly reduced deaths from any cause by 21% compared with placebo (95% Confidence Intervals(CI) 4 to 35, P=0.02). Deaths from stroke were significantly reduced by a relative risk of 39% (95%CI 1 to 62, P=0.05). In the active treatment group, fatal or non-fatal heart failure was reduced by a relative risk of 64% (95%CI 42 to 78, P<0.001) and the rate of any cardiovascular (CV) event was reduced by a relative risk of 34% (95% CI 18 to 47, P<0.001).
There were significantly more adverse events in the placebo group compared with the antihypertensive group (448 vs. 358, P=0.001). Only five events were considered to be treatment-related (three in the placebo group vs. two in the active treatment group).
As highlighted in an accompanying editorial, the decrease in the risk of the primary endpoint, fatal or non-fatal stroke, did not reach statistical significance, nor did the secondary endpoints reduction in deaths from CV or cardiac (MI, heart failure and sudden death) causes. However, the study was stopped early for ethical reasons on the recommendations of an independent monitoring committee, owing to the significant benefit of antihypertensive treatment on death from any cause.
So what?
Antihypertensive treatment with a thiazide-like diuretic (indapamide) and/or an ACE inhibitor (perindopril) has been shown to reduce the risk of death from stroke or any cause in patients aged 80 years or older. It is unclear whether other classes of antihypertensive will have the same benefits. Also, the patients in HYVET were generally healthier than those aged 80 years and over in the general population. The results of the study may not apply to frail elderly people.
Action
Clinicians should continue to follow NICE guidance on the management of hypertension and offer patients over 80 years of age treatment for hypertension. Treatment should be individualised and take into account the preferences and general health of the patient, including any comorbidity and their current drug regimen – which may already be complex. Based on the NICE guidance, MeReC Bulletin Vol.17 no.1 provides an update on the management of hypertension in primary care. Further information on the management of hypertension is available on the cardiovascular disease section of NPC.
Study details
Design: Double-blind randomised controlled trial. It is not clear whether allocation was concealed.
Patients: The study included 3,845 elderly people aged 80 years and over from Europe, China, Australasia and Tunisia, who had persistent high blood pressure (systolic blood pressure [SBP] > 160mmHg). Exclusion criteria included accelerated hypertension, secondary hypertension, haemorrhagic stroke in the last six months, heart failure, signs of poor kidney function, hypo- or hyperkalaemia, gout, clinical dementia and a requirement for nursing care. Participants were told to stop taking antihypertensive medication and take a placebo tablet for at least two months. If average SBP was 160–199mmHg on the second and third follow-up visits people were eligible to enter the study.
Intervention: They were randomised to receive indapamide SR 1.5mg (n=1,933) or matching placebo (n=1,912) with the aim of achieving blood pressure < 150/80mmHg. If blood pressure remained higher than this then perindopril or a second matching placebo could be added. If this additional medication was required for more than three months, the patient was withdrawn from double-blind follow-up with an option to enter open follow-up.
Patients were assessed at least every three months for the first year and at least every six months thereafter. Information was collected on patients’ diseases, medications and blood pressure. Also, patients had blood tests, an electrocardiogram and a cognitive function test.
Outcomes: The primary outcome was fatal or non-fatal stroke, not including transient ischaemic attacks. Secondary outcomes included death from any cause, death from CV causes, death from cardiac causes (MI, heart failure and sudden death) and death from stroke.
Analysis was by intention to treat i.e. patients were analysed in the groups they were assigned to regardless of which medication they actually received and whether they moved to open label treatment.
Results: The groups were well matched. Mean age was 83.6 years, mean blood pressure whilst seated was 173.0/90.8mmHg and 11.8% had a history of CV disease. Median follow-up was 1.8 years.
At two years, 25.8% of the active treatment group were receiving indapamide alone, 23.9% were receiving additional perindopril 2mg and 49.5% were receiving additional perindopril 4mg. At two years, target blood pressure was reached in 48.0% of those in the active treatment group and 19.9% of patients in the placebo group (P<0.001). Also, seated blood pressure was 15.0/6.1mmHg lower in the active treatment group compared with the placebo group.
With regard to the primary endpoint, there were 51 fatal or non-fatal strokes in the active treatment group compared with 69 in the placebo group. However, this difference this did not reach statistical significance, nor did the secondary endpoints reduction in deaths from CV or cardiac causes. Antihypertensive treatment significantly reduced deaths from any cause by 21% compared with placebo (95%CI 4 to 35, P=0.02). Deaths from stroke were significantly reduced by 39% (95%CI 1 to 62, P=0.05). In the active treatment group, fatal or non-fatal heart failure was reduced by 64% (95%CI 42 to 78, P<0.001) and the rate of any CV event was reduced by 34% (95% CI 18 to 47, P<0.001).
There were significantly more adverse events in the placebo group compared with the antihypertensive group (448 vs. 358, P=0.001). Only five events were considered to be treatment related (three in the placebo group vs. two in the active treatment group).
Sponsorship: HYVET was funded by grants from the British Heart Foundation and the Institut de Recherches Internationales Servier.
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