Thursday May 21 2009
Some have recommended that all older people take the drugs
“Blood pressure drugs should be given to everyone over 55 to reduce heart attacks and strokes”, the Daily Mail has reported. The newspaper said the medication should be prescribed even if blood pressure is normal, as new research estimates that common drugs reduce risk of heart attack by a quarter and stroke by a third.
This research was a large, thorough analysis combining the results from a number of trials on blood-pressure-lowering treatments, looking at how medication affected risk of future stroke or heart disease events such as heart attacks. The trials featured data on nearly half a million patients, including people both with and without a history of cardiovascular disease, as well as people with a range of blood pressure levels. These trials collectively demonstrated a reduction in risk of coronary heart disease and stroke regardless of a patient’s history of these conditions or high blood pressure. Based on this, the authors suggest that blood pressure medications should be offered to all people above a certain age, regardless of blood pressure or pre-existing disease.
This was a well conducted study, but its results will need to be considered alongside other issues, such as potential harms, before any change to current treatment practice and recommendations is made.
Where did the story come from?
This research was conducted by Professors MR Law, JK Morris and NJ Wald of the Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine.
No sources of funding were reported for the study, but two of the authors declared holding patents on the formulation of a combined pill to reduce simultaneously four cardiovascular risk factors, including blood pressure. The study was published in the peer-reviewed British Medical Journal.
What kind of scientific study was this?
This was a systematic review and meta-analysis designed to determine how effective different drugs for lowering blood pressure (BP) are for preventing coronary heart disease (CHD) and stroke, and to decide who should receive these treatments.
The researchers searched the Medline database for randomised controlled trials (RCTs) investigating BP-lowering drugs where CHD events (fatal or non-fatal heart attacks or sudden cardiac death) or strokes had been recorded. They included studies published from 1966 to 2007, and excluded trials where patients had kidney failure or where other drugs, such as cholesterol-reducing statin medication, were given as part of the intervention in addition to BP medications.
All RCTs had to have a treatment duration of greater than six months and at least five CHD events or strokes recorded in the study period. Trials could include participants of any age or disease status, and those with prior BP treatment or use of other medications.
From each study, the researchers recorded the number of participants who had a CHD event, stroke or new diagnosis of heart failure or worsening of existing heart failure. Changes in BP in the treated and control groups were also recorded.
The authors categorised the RCTs based on the type of participants recruited: those with no history of CHD or stroke, a history of CHD (heart attack, coronary artery disease without recent heart attack or heart failure) or a history of stroke. In trials where the participants had no history of CHD or stroke, they usually had high BP and were usually being treated to reach a target BP.
The authors also categorised trials into:
- ‘Blood pressure difference trials’, which aimed to achieve a difference in BP between those randomised to the study drug and those receiving control (placebo or non-treatment) and show the effect this had on the incidence of CHD events and stroke.
- ‘Drug comparison trials’, where two different BP-lowering drugs were compared, and the aim was not to demonstrate a difference in BP between the groups, but to look at other effects of the treatments.
The researchers pooled the results of the trials using meta-analysis. In their analysis they also looked at the effect that taking one or more BP drug had on CHD and stroke risk according to age group and pre-existing BP status. In order to estimate the possible effect of BP medications at different doses, the authors combined their results with the results from a meta-analysis of placebo controlled RCTs looking at the effects of different doses of BP drugs and with data from the largest meta-analysis to date of epidemiological cohort studies observing how blood pressure changes affected risk of CHD events and stroke.
What were the results of the study?
Of the selected RCTs:
- 108 were ‘blood pressure difference trials’ (248,445 subjects),
- 46 were ‘drug comparison trials’ (230,491 subjects), and
- seven fell into both of these categories.
The trials included a total of 464,164 people divided into the three categories. The trials covered a total of 22,115 CHD events and 12,034 strokes. The average age of participants across all trials was 64 years.
Looking at the blood pressure difference trials, beta-blocker drugs were beneficial for reducing BP compared to a control treatment, but also for reducing risk of a further CHD event in those with a prior history of CHD (across all groups they gave an overall 29% reduction in risk compared to 15% in other drugs trialled). However, this benefit was mainly in those who were taking the beta-blocker following a heart attack in the previous few years, for whom their risk reduction of another CHD event was 31%. This risk reduction was only 13% for those who had a history of CHD but had not had a recent heart attack. Beta-blockers gave no significant reduction in CHD risk for those with no history of cardiovascular disease.
In all blood pressure difference trials (excluding trials of beta-blockers in CHD patients), reduction in systolic BP by 10mmHg, or reduction in diastolic BP by 5mmHg, reduced overall risk of CHD events by 22% and risk of stroke by 41%.
All classes of BP-lowering drugs (beta-blockers, angiotensin converting enzyme (ACE)-inhibitors, angiotensin receptor blockers, calcium channel blockers and thiazides) had a similar effect in reducing risk of CHD events and stroke, although calcium channel blockers reduced risk of stroke more than the other drugs.
Across all classes of drugs, risk reduction for CHD events and stroke was found to be similar in those with a history of CHD or stroke and those without prior cardiovascular disease, and also regardless of the BP level prior to treatment. This risk reduction extended to individuals not classified as having high blood pressure. The meta-analysis additionally showed that risk of heart failure was reduced by 19% by calcium channel blockers and 24% by all other drugs.
The researchers combined their results with a previous meta-analysis of cohort studies and with trials determining BP-lowering effect of different doses of the same drug. From this they found that three drugs given in combination at half standard dose reduced the risk of CHD by about 46% and of stroke by about 62% in people aged 60 to 69 (the age group generally covered by trials) who had a pre-treatment diastolic BP of 90mmHg. One drug at standard dose reduced CHD and stroke risk by about half this amount.
What interpretations did the researchers draw from these results?
The authors conclude that all classes of BP-lowering drugs have a similar effect in reducing risk of CHD events and stroke in relation to a given reduction in blood pressure. Calcium channel blockers appear to be slightly more effective than other drugs in preventing stroke, and beta-blockers appear to have added benefit in reducing further CHD events when taken in the immediate post-heart-attack period. The reduction in CHD and stroke appears to be similar regardless of pre-treatment BP and the presence or absence of existing cardiovascular disease.
The authors say that their results highlight the importance of lowering blood pressure in everyone above a certain age, rather than measuring BP and only treating it if it is elevated.
What does the NHS Knowledge Service make of this study?
This was a large and thorough meta-analysis that has examined trials of blood-pressure-lowering treatments and evaluated how they affect future risk of heart disease events (such as heart attack) or stroke. The trials included both people with a history of cardiovascular disease and those without, as well as people with a range of pre-treatment blood pressure levels. Collectively, these trials have demonstrated a reduction in risk of CHD and stroke through use of any medication to lower blood pressure, regardless of prior history or existing blood-pressure levels.
As the authors say, the combined results of the blood pressure difference trials demonstrated that a 10mmHg reduction in systolic pressure or a 5mmHg reduction in diastolic pressure reduced risk of CHD by 22% and stroke by 41%. These findings are consistent with results of a previous large meta-analysis of cohort studies, in which similar blood pressure reductions resulted in CHD risk being reduced by 25% and stroke risk being reduced by 30%.
The results of this review point to there being a benefit of disease prevention through lowering blood pressure, and this benefit did not seem to be affected by blood pressure at the start of the trial. From this, the authors suggest that guidelines may need to be changed so that the reviewed medications are offered to all people above a certain age, regardless of blood pressure or pre-existing disease.
A few points to note include:
- Meta-analysis can involve combining results of trials with different methods, study populations, follow-up and measured outcomes. This can create some inaccuracy in the quantified risk estimates.
- As the authors mention, across all trials, 25% of those allocated to take the study medication discontinued their treatment, which will affect the accuracy of the estimated effect of the drugs.
- Although some trials did include people with normal BP, most participants with no history of cardiovascular disease had elevated BP. Therefore, the study does not include wide representation of healthy people with normal BP and no other risk factors for cardiovascular disease.
- In people without history of cardiovascular disease there was not always an observed benefit in risk reduction.
- All medications carry the risk of adverse effects, and this must be taken into account when considering offering medications to a whole age group, including those who may have other medical conditions or take treatments that would make anti-BP medication unsuitable.
- Blood pressure is not the only risk factor for heart disease or stroke. Genetic factors, gender, smoking, raised cholesterol, obesity and diabetes are all factors that contribute to disease risk, and prevention strategies would ideally take into account all of these factors.
These review findings will undoubtedly prove invaluable, and are likely to lead to further study and consideration of the current treatment and practice for these common, serious conditions.