“Treating the over-80s with blood pressure drugs can cut death rates by 21 per cent, study shows” is the headline in the Daily Mail today. It reports that although other studies have suggested that the over-80s may be harmed by medication for high blood pressure, this study found “lowering blood pressure in the over-80s cut their death rate by a fifth and heart attacks by a third”.
The reports are based on a large, well-conducted study, which provided reliable results. However, this study only looked at one particular type of diuretic blood-pressure medication in the over 80s. It may not apply to all ‘antihypertensives’.
Where did the story come from?
Dr Nigel Beckett and colleagues of the Hypertension in the Very Elderly Trial (HYVET) study group carried out this research at 195 centres in Europe, China, Australasia and Tunisia. The study was funded by the British Heart Foundation and the Institut de Recherches Internationales Servier. It was published in the New England Journal of Medicine , a peer-reviewed medical journal.
What kind of scientific study was this?
This was a double-blind randomised controlled trial designed to investigate whether using antihypertensive drugs in people aged over 80 years reduces the risk of stroke or death from other causes.
The researchers enrolled elderly people (aged 80 and above) from Europe, China, Australasia and Tunisia whose medical records confirmed that they had persistent high blood pressure (systolic blood pressure (SBP) of 160mmHg or more). People who had heart failure, haemorrhagic stroke in the past six months, gout, clinical dementia, signs of poor kidney function or needed nursing home care were not eligible to participate. The people who were included were told to stop taking their current high blood pressure medication for at least two months and were given a placebo tablet instead. Their blood pressure was measured twice at the start of this period, and then later at one and two months. If the average blood pressure on the second and third visits was between 160 and 199 mmHg then they were eligible to be included in the study.
The 3,845 people who were eligible were randomly assigned to receive either the diuretic indapamide (1.5mg sustained release pills) or an inactive placebo. The aim of treatment was to reduce blood pressure to less than 150 mmHg systolic/80 mmHg diastolic. If the blood pressure remained higher than this, then the participants in the indapamide group could have another drug added to their treatment, the angiotensin converting enzyme (ACE) inhibitor perindopril (2mg or 4mg). Participants in the placebo group could be given additional placebo. If this additional medication was needed for longer than three months, the patient was withdrawn from double blind treatment, but could continue to receive treatments without blinding.
Participants were also withdrawn if they were receiving the top dose of the study medications but had a systolic blood pressure of 220 mmHg or above while sitting or a diastolic blood pressure of 110mm Hg or above while sitting on two or more consecutive visits over a month or longer.
Researchers assessed patients at least every three months in the first year, then at least every six months after this. Information was collected on patients’ medications, other diseases and blood pressure at these appointments. In addition, once a year blood samples were taken for testing, and patients had an electrocardiogram (ECG) and a cognitive function test.
The researchers followed up the participants to see whether the proportion of people who experienced a stroke (either fatal or non-fatal) differed between the groups. This was the main outcome they were interested in. They also collected information on heart failure and death from any cause, from stroke, from cardiovascular causes and from cardiac causes. People were analysed in the groups they had been allocated to, regardless of what medication they actually received and whether they had to move to open-label treatment.
What were the results of the study?
Participants’ ages ranged from 80 to 105 years, and they were followed for 1.8 years on average (median). At two years, about 50% of people in the indapamide group were also receiving 4mg perindopril and 24% were receiving 2mg perindopril. At two years, blood pressure was lower in the indapamide group than the placebo group, and 48% of the indapamide group reached the target blood pressure, compared with about 20% in the placebo group.
There were 51 strokes (fatal and non-fatal) in the indapamide group compared with 69 in the placebo group. This represented a 30% reduction, but it did not quite reach statistical significance.
Antihypertensive treatment significantly reduced deaths from any cause by 21% compared with placebo. It also significantly reduced heart failure (fatal and non-fatal) by 64%. There was a strong trend for reduction of fatal strokes (39% reduction) and deaths from cardiovascular causes (23% reduction). However, these reductions did not quite reach statistical significance.
There were more adverse events reported in the placebo group than the antihypertensive group (448 compared with 358). Only five of these events were thought to be related to the treatment received (three in the placebo group and two with treatment). The trial ended earlier than planned because of the reduction in death from all causes.
What interpretations did the researchers draw from these results?
The researchers concluded that antihypertensive treatment based on sustained release indapamide, with or without perindopril, reduces the risk of death in very elderly patients.
What does the NHS Knowledge Service make of this study?
This was a large and well-conducted study with reliable results. There are some potential limitations, which the authors acknowledge:
- Due to the selection criteria applied during enrolment, the participants in the trial were healthier than very elderly people as a whole. These results may not apply to more frail people.
- Cause of death may be difficult to establish in this population, particularly among people who die alone at home without any preceding illness, and in those who do not undergo autopsy. Rapid and unexpected deaths in this trial were classified as deaths from cardiovascular disorder. These factors may have resulted in the under-reporting of deaths from stroke.
- The study has only examined the use of one particular type of diuretic blood pressure medication in the over-80s. Results should not be generalised to ‘antihypertensives’ as a whole, as this constitutes a wide range of medications.
Sir Muir Gray adds...
Artificial limits are often imposed by the need to design treatment trials. These often have an arbitrary upper age limit and need to supplemented by other studies which focus on people above that age. There is no age at which people change from one type of person to another.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Guardian, 1 April 2008
Daily Mail, 1 April 2008
Channel 4 News, 1 April 2008
The Scotsman, 1 April 2008
Links to the science
N Eng J Med 2008; Mar 31 [Epub ahead of print]
Cochrane Database Syst Rev 1998, Issue 2