Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies
BMJ 2009; 338 doi: https://doi.org/10.1136/bmj.b1665 (Published 19 May 2009) Cite this as: BMJ 2009;338:b1665All rapid responses
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This debate very much parallels that with statins and cholesterol.
Lowering LDL cholesterol,like lowering blood pressure, will almost always
lower the risk of cardiovascular events, and the relative risk reduction
will be similar regardless of starting BP or LDL level. But the absolute
risk for people with say a systolic BP of 135 and no other risk factors is
very low and you will have to treat scores if not hundreds of people like
this for several years to prevent one event. But, firstly, I find as many
others must who treat hypertensive patients, that many are not keen on any
sort of medication, even with systolic BPs well above 160. I am not at all
sure that we can persuade such people that they should be taking any
medicines at all when their BP is 30 mm less than this. Secondly, this
might still be fine if antihypertensive drugs were totally innocuous. It
is true that serious and dangerous adverse effects are rare but unpleasant
and inconvenient ones are common and can put patients off the idea of
treatment altogether. They may be "minor" for doctors and drug
manufacturers but may be less so if they follow this advice and actually
take the same pills. This may be a new way to manage hypertension, or
rather blood pressure, but how about thosr who are supposed to take the
medicine?One can't help feeling that this type of recommendation tend to
come from those who don't spend a great deal of their time in clinics or
surgeries.
Competing interests:
None declared
Competing interests: No competing interests
Dr Bower's list of questions for his GP should be provided to all
patients who are offered the new panacea, and the suggested treatment
witheld until the patient declares him or herself satisfied.
Unfortunately, what will happen is that the GP will declare that the
"Experts" have decreed it is the right thing to do, and who is he (or she)
to question this advice from on high- especially if is endorsed by
financial incentives (QOFs.)
There are, of course, many difficulties in interpreting results from
trials, not the least of which is the fact that the results apply to a
situation in the past which no longer exists, and to a population with
different risk estimates- clearly demonstrated by the exaggerated risks of
the Framingham figures for the present UK population. All this supports
the view that advice from on high needs to be taken with a pinch (but no
more, mind!) of salt.
Competing interests:
None declared
Competing interests: No competing interests
Before I start taking blood pressure pills to reduce my currently
normal blood pressure, there are just a few questions I would want to ask
my doctor. What is my risk of dying, of anything, not just heart attacks
or strokes in the next 10 or 20 years? What would be the absolute risk
reduction of death as a result of taking medication? What is my current
risk of any major morbidity, and how would this be affected by medication?
What are the numbers needed to treat, and what are the numbers needed to
harm?
Have Law et al presented this information, so that my doctor can answer my
questions? If not, I wonder whether they may be premature is stating that
they have demonstrated “the value of blood pressure lowering treatment to
everyone in a population above a particular age.”
Competing interests:
None declared
Competing interests: No competing interests
The boldest claim of this study regards the importance of treatment
of stage 1 pre-hypertension, stage 2 pre-hypertension, and let's say
normal range blood pressure in older individuals.
Yet, I can not find web figures 5a-1 and 6a-m which they claim
support this proposal. I would appreciate a complete summary of the
number of patients, pre-treatment blood pressures and treatment effects
and outcomes that supports this idea.
I'm ok with their stated conflict of interest in that they have
patents or patents pending for a polypill. But, the 1/2 dose, multiple
pill approach data seems just to be a statistical extrapolation or guess
rather than any real data.
Please clarify.
Competing interests:
None declared
Competing interests: No competing interests
The authors found 108 pressure drugs studies controlled by placebo or
by a non treated group. That would have allowed the reporting of numbers
needed or needlessly treated for average treatment periods, rather than
just relative or percentage risk reductions.
Specifically regarding all-cause mortality, the authors state: "There
were statistically significant reductions in all cause mortality in all
[108 that would be] the blood pressure trials .." at a relative risk of
0.87. Could the authors clarify this statement and report on the numbers
needed to treat to postpone one death and over which treatment period.
Competing interests:
None declared
Competing interests: No competing interests
Law et al make a good case for believing that benefits of BP
reduction will accrue across a range of patients, if at sufficiently high
CVD risk to make it worth their while swallowing a Pill-a-day.
Low-dose Aspirin fulfils this role, and meets the 'fire-and-forget'
ideal of not requiring any follow-up, nor dose adjustment, nor any
laboratory monitoring. It does however have to be prescribed with
caution, and a regard to its risks and contraindications.
Simvastatin is fast approaching the Aspirin gold-standard, being
equally cheap , safe and effective. It works without regard to initial
cholesterol, and monitoring of acheived cholesterol targets can be
disregarded in favour of a pragmatic highest-tolerable-dose rule. Very
little harm is likely to occur with statin in the polypill, and so long as
only those patients at high CVD risk are treated, it should prove very
cost-effective.
But does Law et al.'s argument extend to low-dose hypotensive agents
?? I think not - or not yet.
Law et al refer to meta-analysed data which excluded all those
patients with initial normal BPs, yet they state 'Our results indicate
that the use of blood pressure lowering drugs should not be limited to
people with high blood pressure.' They go on to mention 'The proportional
reduction in disease events for a given blood pressure reduction was the
same irrespective of blood pressure before treatment (fig 5), down to
levels of 70 mm Hg (or lower) for diastolic blood pressure..'
I fear that giving a hypotensive agent to someone with a BP of
100/60, say - is likely to do more harm than good, and I would want RCT
evidence before I treat 'normotensives'. I might dub this "Law's flaw".
Law et al subconsciously acknowledge this concern by advocating low doses
.. but their combinations defeat this caution.
I am persuaded that a first-check-then-fire-but-not-forget approach
should be adopted, ie:
1. Check CVD risk assessment ( Age and Sex alone might be sufficient)
2. Offer Smoking cessation, Aspirin, Statin
3. Measure BP ( ? and cholesterol ?? )
4. Treat those above say 140/70, if CVD, or CVD risk >20%. ( If
CVD risk is less than 20% then BP-lowering has a low-yield with very high
NNT )
5. Recall once a year, for QOF and quality.
Frankly, that's what I do now.
Competing interests:
beneficence vs. non-maleficence
Competing interests: No competing interests
High blood pressure is the most important modifiable risk factor for
stroke. High blood pressure is a potent risk factor, but it almost never
produces detectable symptoms. There is now strong evidence from randomized
trials that blood pressure-lowering treatment is one of the most effective
and generalizable strategies for secondary prevention of stroke. This
review from Law, et.al. confirm that lowering high blood pressure will be
beneficial for preventing further stroke. Once the patient with stroke has
stabilized, all patients should receive blood pressure-lowering therapy,
irrespective of their blood pressure levels. Currently, the most important
goal in primary and secondary prevention of stroke is a strict
normotensive blood pressure control. Antihypertensive treatment is
recommended for both prevention of recurrent stroke and prevention of
other vascular events in individuals who have had an ischaemic stroke or
TIA. Nevertheless, there has been a concern that lowering BP below a
certain threshold in patients with established carotid or vertebrobasilar
stenosis or occlusion might cause reduced cerebral blood flow. Many open
questions remain of stroke research needs in the future.
Competing interests:
None declared
Competing interests: No competing interests
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Impressive and provocative, but . . .
I would imagine that much, if not the lion's share, of the data which
the
study draws on derive from studies of patients with hypertension; is there
any outcome or tolerability data from large trials of antihypertensives in
normotensive people?
If not, to adopt the recommendations of Law et al would involve the
classic
error of generalising from one population to another - in this case, from
the
hypertensive to the normotensive population.
Futhermore, from the perspective of the individual patient and the
individual
primary care physician, however, things look different. Patients
prescribed
antihypertensives are likely to feel medicalised, and a substantial number
are
likely to interpret any number of temporally-related physical changes as
being due to the drug, whether physiologically plausible (dizziness,
cough,
erectile dysfunction, oedema, polyuria, rash) or not (any primary care
doctor
can provide multiple examples, I'm sure!); they will return for medication
changes, reassurance, further evaluation, diverting resources which might
be
better used elsewhere
Competing interests:
None declared
Competing interests: No competing interests