Bruce - you are correct that older rcts of treating hypertension in younger
people (<60 yrs) show substantial benefit for stroke but less for CHD.
More recent trials in older people using lower doses of diuretics and beta
blockers show RRRs for stroke in the order of 35% and CHD about 25% -which
is similar to the expected effect from observational studies examing the
difference in risk in people with long term exposure to different bp
levels. There are lots of meta-analyses around for example Insua et al Ann
Intern Med 1994; 121:355-62 which includes people over 60 yrs. As by far
the majority of treated hypertensives are over 60 yrs, this is the relevant
group. Moreover, it is likely, although I cannot prove it, that the
improved RRRs in recent trials is probably related to lower doses leading
to lower side effect levels and great compliance.
Regarding the cohort study you quote,and there are others, these non
randomised studies are seriously flawed and are totally inappropriate for
investigating the effect of treatments because of indication bias. Just
about every cohort study examing the treatment of raised blood pressure
shows a higher CVD risk in the treated group whereas every RCT shows the
opposite. This is a perfect example of confounding due to doctors
appropriately choosing to treat patients at high risk. Unfortunately many
of the characteristics (generally qualitative) that doctors use to
characterise high risk patients are not captured in the standard risk
factors (interesting docs are bad at targetting high risk patients using
the easy indicators like the standard risk factors) and these more
qualitative factors cannot be adjusted for in analyses. This is the reason
why therapy questions are best addressed by RCTs. Unless the RRs from
observational studies examining therapy are very large and the
investigators are very confidant thay have dealt with confounding (which is
seldom possible) then one must be very cautious in interpreting non
randomised studies of treatment.
Rod
>
>Re: reversibility of cardiovascular risk
>
>> Dear Bruce - I have responded to others who have asked about reversibility
>> -see my response to Toby Lipman:
>>
>> "Toby - Yes, I am saying that the difference in absolute risk between the
>> early and late treated hypertensives will be very small and so the NNT very
>> large. The evidence comes from comparing the effect of treatment in RCTs
>> compared with the estimated difference in risk in cohort studies. What we
>> find is that the predicted effect of lonterm differences in risk from
>> cohort studies is very similar to the actual effects observed in trials."
>
>My understanding of the trial evidence for hypertension is that
>although it's an important risk factor for cardiac disease in cohort
>studies, most of the effect in treatment trials is on stroke not CHD.
>As I understood it, in the elderly you can show effects on CHD,
>but in younger people you can't. One study I saw last year ( BMJ
>1998; 317: 167-171) following a cohort of treated hypertensives
>(said to be well controlled) and compared them to a matched control
>group (not well described) and found double the cardiac mortality at
>20 years in the hypertensives.
>
>I've just quickly looked at the MRC trial of treatment of mild HT
>again (17, 354 35-64 year olds with diastolics 90- 105) where you get
>a small but significant decrease in stroke (RRR 45%, ARR
>0.12%/patient year). There is no effect on coronary events - 222
>in treatment group, 234 in placebo so the effect on all
>cardiovascular events is solely due to the effect on stroke.
>
>Forgive me if I'm being slow. I suspect there may be a meta-analysis
>or similar somewhere which deals with this and I'd be interested in
>any reference.
>
>Thanks
>
>Bruce
>
>Bruce Guthrie,
>MRC Training Fellow in Health Services Research,
>Department of General Practice,
>University of Edinburgh,
>20 West Richmond Street,
>Edinburgh EH8 9DX
>Tel 0131 650 9237
>e-mail [log in to unmask]
Dr Rodney Jackson MBChB PhD FAFPHM
Associate Professor of Epidemiology
Head of Department
Dpt of Community Health, School of Medicine
University of Auckland
(Grafton Mews, 52-54 Grafton Rd)
Private Bag 92019, Auckland, New Zealand
Phone: +64 (0)9-3737599 ext 6343
Fax: +64 (0)9-3737503
e-mail: [log in to unmask]
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