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Merit of using risk reduction rather than absolute risk for lipid lowering drugs
EDITOR The chance of preventing a coronary event is the absolute risk
multiplied by the relative risk reduction, but the question is whether
the relative risk reduction is equal in patients of all ages. The
meta-analysis of the statin trials by LaRosa et al,2 cited
as evidence for this by Jackson (together with three hypertension
trials), does not render Law et al's meta-analysis of lipid lowering
trials invalid3 as LaRosa et al included both primary and
secondary prevention trials, assuming that the difference between them
relates only to the absolute risk of a further event.
Our study concerned primary prevention, and the two relevant statin
trials in this meta-analysis suggest that age may influence risk
reduction, although formal statistical analyses were not reported. One
of these trials showed a relative risk reduction of 40% (95%
confidence interval 16% to 56%) below the age of 55, compared with
27% (8% to 43%) above4; the other study showed a 46.5%
risk reduction below the median age (age 58) compared with 30.4%
above.5 Both trials were consistent with the age effect
predicted by Law et al's meta-analysis.
Our objective was to highlight the potential for leaving young patients
with multiple risk factors untreated by assuming that relative risk
reduction is not influenced by age. If treatment is based solely on
absolute risk a male, non-smoking, diabetic patient with systolic blood
pressure of 180 mm Hg and total and high density lipoprotein
cholesterol concentrations of 6.0 and 0.9 mmol/l would not reach the
risk threshold for treatment until the age of 53. By contrast, after
adjustment for age a risk reduction threshold of 4.5% is reached at
age 42 when absolute risk is 8.9%.
During this 11 years the patient's average annual risk of
coronary heart disease is approximately 2.4%, giving a cumulative event risk of 27.5%, or more than a 1 in 4 chance of an event through
the delay in treatment. If this was adjusted for life years gained The aim of treatment recommendations should be to maximise use of trial
data to increase their relevance. Use of computer based technology
enables complex guidelines to be handled easily in a clinical setting
and readily updated as new evidence becomes available.
Our study of whether treatment recommendations for lipid
lowering drugs should be based on absolute coronary risk or risk
reduction1 was accompanied by an editorial by Jackson in
the same issue that warrants further discussion.
as
suggested in both our study and Baker et al's study published in the
same issue6
the benefit of starting treatment at an early
age would become even more apparent.
nearrh{at}netscape.net
Sud Ramachandran
North Staffordshire Hospital Trust, North Staffordshire
Hospital, Stoke-on-Trent ST4 6QG
| 1. |
Ramachandran S, French JM, Vanderpump MPJ, Croft P, Neary RH.
Should treatment recommendations for lipid lowering drugs be based on absolute coronary risk or risk reduction?
BMJ
2000;
320:
677-678 |
| 2. |
LaRosa JC, He J, Vupputuri S.
Effect of statins on risk of coronary disease: meta-analysis of randomized controlled trials.
JAMA
1999;
282:
2340-2346 |
| 3. |
Law MR, Wald NJ, Thompson SG.
By how much and how quickly does reduction in serum cholesterol lower risk of ischaemic heart disease?
BMJ
1994;
308:
367-372 |
| 4. | West of Scotland Coronary Prevention Group. West of Scotland coronary prevention study: identification of high-risk groups and comparison with other cardiovascular intervention trials. Lancet 1996; 348: 1339-1342[CrossRef][Medline]. |
| 5. |
Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al.
Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. Results of AFCAPS/TexCAPS.
JAMA
1998;
279:
1615-1622 |
| 6. |
Baker S, Priest P, Jackson R.
Using thresholds based on risk of cardiovascular disease to target treatment for hypertension: modelling events averted and number treated.
BMJ
2000;
320:
680-685 |
Joint British societies recommend their computer program for risk calculations
EDITOR We have therefore compared the accuracy of the new Sheffield tables,
the joint British societies' charts for coronary risk,3 and the New Zealand charts for cardiovascular risk4 with
the Framingham risk equation on which they are based. We calculated them for a series of 386 patients referred to our lipid clinic for
advice about whether drug treatment was justified. The joint British
societies' charts identified correctly 88% of the patients to whom
they could be applied, the new Sheffield tables 81%, but the New
Zealand charts only 63%.
Although they are therefore similar in terms of accuracy, the new
Sheffield tables were not adopted by the joint British
societies3; they do not allow practitioners to judge the
level of risk between 15% and 30%, and these guidelines recommend
that, as statins become cheaper and more resources are available,
people at lower risk will progressively be targeted for cholesterol
lowering treatment. This decision seems to be further justified by
Isles et al's finding that nurses and doctors found the new Sheffield
tables difficult to use.5
Rather than tables or charts, the joint British societies recommended a
computer program available from us, from the British Heart Foundation,
or on the British Hypertension Society's website (www.hyp.ac.uk/bhs).2 This program provides the risk of
both coronary heart disease and stroke for both systolic and diastolic blood pressure, thus allowing a more comprehensive understanding of
cardiovascular risk and rational planning of antihypertensive and lipid
lowering treatment.
Absolute cardiovascular risk is not most appropriate measure to
use
EDITOR It is precisely because each year of life is equally valuable that
death becomes less of a tragedy as one becomes older. A 40 year old who
dies of a heart attack may lose 40 years of potential life; this is
unlikely to be the case for an 80 year old. This also fits in with the
public perception. Even the most hardened undertaker will cry when
faced with a child's body to bury or cremate: it is the thought of all
the future that might have been.
To use risk prediction charts or computer programs to bring
everyone's risk down to the same level will maximise the number of
lives saved but not the amount of life saved. It will provide quick
results to please NHS planners, and it will divert much NHS funding
into selected pharmaceutical companies, but the impact will be on those
near the end of their lives anyway. It will have relatively little
effect on the epidemic of people dying in middle age from heart disease.
To achieve a proper balance we need to treat the young more, and the
old less, than the charts suggest. Remember that a 40 year old with a
30% risk of death over 10 years will have a 70% chance of reaching
50, a 49% chance of reaching 60, and only a 34.3% chance of reaching
70 if no action is taken.
Having so many different guidelines about reducing risk is
confusing
EDITOR I want a simple chart or computer program that will allow me to assess
and reduce the risk of cardiovascular disease in patients who may or
may not already be taking hypotensive treatment. I also wish to give
patients some idea of the likely benefit they can expect from
treatment. If I have understood things correctly the following five
statements are true.
So, until someone can clear the waters for me, I think I'll just
continue to muddle along. Despite my apparent lack of enthusiasm for
the cardiovascular cutting edge I can be contacted on email.
Subclinical hypothyroidism is risk factor for coronary heart
disease
EDITOR It has been obvious to many clinicians that subclinical hypothyroidism
is a risk factor for coronary heart disease in women,2 and
now the large Rotterdam population study has confirmed that it is an
independent risk factor as important as the other risk factors for
coronary heart disease.3 Nowhere is this fact mentioned despite its obvious importance for prevention.
By including high density lipoprotein cholesterol
concentrations the new Sheffield tables are considerably more accurate than the earlier version.
1 2
We disagree, however, with
the assessment of the accuracy of risk prediction methods by applying them to the whole population when such methods are intended to identify
high risk populations. Inevitably, when a whole-population approach is
used most people will have a risk that is substantially below the high
threshold risk for which the tables are designed. Accuracy should be
tested in people who are closer to this threshold because they are
the type of patient for whom the clinical decision about drug treatment
is to be made in practice.
Department of Medicine, Manchester Royal Infirmary, University
of Manchester, Manchester M13 9WL pdurrington{at}hq.cmht.nwest.nhs.uk
1.
Wallis EJ, Ramsay LE, Haq IU, Ghahramani P, Jackson PR, Rowland-Yeo K, et al.
Coronary and cardiovascular risk estimation for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population.
BMJ
2000;
320:
671-676 2.
Durrington PN, Prais H, Bhatnagar D, France M, Crowley V, Khan J, et al.
Indications for cholesterol-lowering medication: comparison of risk-assessment methods.
Lancet
1999;
353:
278-281[CrossRef][Medline].
3.
Wood D, Durrington PN, Poulter N, McInnes G, Rees A, Wray R.
Joint British recommendations on prevention of coronary heart disease in clinical practice.
Heart
1998;
80(suppl 2):
S1-29 4.
Dyslipidaemia Advisory Group, on behalf of the scientific committee of the National Heart Foundation of New Zealand.
National Heart Foundation guidelines for the assessment and management of dyslipidaemia.
N Z Med J
1996;
109:
224-232[Medline].
5.
Isles CG, Ritchie LD, Murchie P, Norrie J.
Risk assessment in primary prevention of coronary heart disease: randomised comparison of three scoring methods.
BMJ
2000;
320:
690-691
The BMJ issue of 11 March has reduction of risk
factors for ischaemic heart disease as its theme.1 In each
of the papers reduction in the absolute risk is described as an
appropriate goal. It is not. Absolute risk
the chance of dying or
developing serious symptomatic ischaemic heart disease for the first
time
has a different value at different ages. This is not because
people of different ages should have a different value attached to
their life (in my view all life is equally valuable); rather it is
because it is a measure of death and not of life.
Fountain Medical Centre, Morley, Leeds LS27 9EN
daniel{at}albert4.demon.co.uk
1.
Risk in cardiovascular disease [theme issue].
BMJ 2000;320 (7236). (11 March.)
The 11 March issue of the BMJ provided a
wealth of information and advice on how we might best bring some
logical order into our efforts to reduce cardiovascular risk in the
population.1 As a reasonably conscientious general
practitioner, I read all the relevant papers (some of them twice) and
the accompanying editorial, yet I came away feeling that I was
floundering around in a muddy present rather than striding out into a
brave new evidence based future.
Dougal Jeffries
Bemerton Heath Surgery, Salisbury SP2 9DJ
dougal.j{at}virgin.net
1.
Risk in cardiovascular disease [theme issue].
BMJ 2000;320 (7236). (11 March.)
The BMJ issue of 11 March is concerned with the risk
factors for cardiovascular disease.1 At a rough count
there are 10 items on these, with 33 named contributors and the
combined strength of the British Cardiac Society, British
Hyperlipidaemia Association, British Hypertension Society, and British
Diabetic Association.
152 Harley Street, London W1NN 1HH
1.
Risk in cardiovascular disease [theme issue].
BMJ 2000;320 (7236). (11 March.)
2.
Fowler PBS, Swale J, Andrews H.
Hypercholesterolaemia in borderline hypothyroidism. Stage of pre-myxoedema.
Lancet
1970;
ii:
488-491.
3.
Hak AE, Pols HAP, Visser TJ, Drexhage HA, Hofman A, Witteman JCM.
Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam study.
Ann Intern Med
2000;
132:
270-278
© BMJ 2000
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