How should we balance individual and population benefits of statins for preventing cardiovascular disease?BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.c6244 (Published 26 January 2011) Cite this as: BMJ 2011;342:c6244
All rapid responses
Dear Sir or Madam:
Regarding the 5 Feb 2011 BMJ article by Kamsesh Khunti et al, I
offer the following thoughts regarding the concept of "the worried well"
when it applies to coronary artery disease in the general population.
Most people, men more than women, have coronary artery plaque which has
been being laid down since early adulthood. I think most would agree that
this a pathological process, not a normal part of aging. Since for men,
the numerically most common first clinical manifestation of coronary
artery disease is myocardial infarction, one could take the position that
it is intellectually dishonest and unjustifiably dismissive to refer to a
person who is aware that they have coronary artery plaques, that (for most
people) they are slowly progressive, and who is concerned about this
situation, as "worried well" right up until the point that their clot
forms and their ischaemic chest pain begins. One could take the position
that these peopla are not well; they have a progressive, potentially fatal
pathological process taking place within their bodies. Kamsesh Khunti et
al note that risk prediction is, as far as the individual is concerned,
hugely unsatisfactory. Knowing that a serum cholesterol level is a poor
predictors of risk, and that people with normal cholesterol levels
routinely have myocardial infarctions, a person on the street might
rightly assert that withholding statins until they have had their heart
attack is the worse kind of closing the door after the horse has bolted,
especially since we know that the horse is trying to escape.
Dr J D Stevenson MPH, FRAeS
Wyton, Cambridgeshire, PE28 2JR
Competing interests: No competing interests
Hingorani and Hemingway are advocating that we put millions more
healthy people on long term statin therapy in an attempt to prevent some
people from dying of heart disease. This approach is analogous to locking
up all young men in order to reduce the crime figures. It might have some
merit were there any good evidence that statins prevent healthy people
from dying prematurely: but there is not.
One problem is that very few trials have been about pure primary
prevention. This is because the effects are so small in healthy
populations that the researchers have had to include some unhealthy ones
to ensure that enough people die during the trial period. The oft-quoted
WOSCOPS(1) study included subjects with stable angina and intermittent
claudication. Despite enrolling over six thousand subjects and following
them up for 5 years it failed to show a significant effect on all cause
mortality.(Don't be seduced by figures on cardiovascular mortality. There
is not point in being spared a fatal heart attack only to be killed in
some other way by the treatment. )
By pooling results from many trials, metanalyses attempt to show
effects where individual trials have failed. The recent Cochrane review(2)
highlighted some of the limitations of existing trial evidence. The
authors complained about "selective reporting of outcomes, failure to
report adverse effects and inclusion of people with cardiovascular
disease". They included in their analysis trials where up to 10% of the
participants had pre-existing cardiovascular disease. Even then the effect
on mortality was minimal: one death prevented every 588 person years. (31%
of the weight of this metanalysis comes from the WOSCOPs trial.)
Another problem with the trials is bias. Many trials are not properly
blinded. For example clinicians treating subjects will usually know their
lipid parameters, and easily guess whether they receiving active treatment
or placebo. Therapeutics Initiative(3) found that, when trials subject to
bias were removed from the equation, the effect on mortality disappeared.
They concluded that "statins do not have a proven net health benefit in
primary prevention populations and do not represent a good use of scarce
There are enough previously well people already hopelessly
medicalised by statin treatment, subjected to the cost and anxiety of
frequent visits to the doctor, regular blood tests, and collection of
repeat prescriptions, not to mention the many who endure muscle aches and
pains, not realising it is due to their tablets. And all because their GP
has thoughtlessly put them on statins in the misguided belief that their
cholesterol level was "too high" Let us not make the situation worse by
lowering the threshold for treatment.
1)Shepherd J et al. Prevention of coronary heart disease with
pravastatin in men with hypercholesterolemia. West of Scotland Coronary
Prevention Study Group.
N Engl J Med 1995 Nov 16;333(20):1301-7.
2)Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP,
Statins for the primary prevention of cardiovascular disease (Review)
Cochrane Database Syst Rev. 2011 Jan 19;1:CD004816.
3)Therapeutics Initiative. University of British Columbia. Do statins
have a role inprimary prevention: an update. Therapeutics letter 77.
Competing interests: No competing interests
Should we refocus the debate on cardiovascular risk factors and mortality, to elevate the importance of physical activity and cardiorespiratory fitness?
Our research (1) has shown that in schizophrenia, patients lose up to
25 years of life expectancy. We identified the top 4 mortality risk
factors as low fitness, hypertension, smoking and diabetes mellitus. The
World Health Organisation (2) identified these same top 4 risk mortality
factors in the general population. Blair (3) reported that physical
inactivity / low cardiorespiratory fitness was the major public health
risk for all cause mortality in western society. Moreover, he highlighted
a failure of primary care to assess this risk factor with its focus on
traditional risk factors (hypertension, cholesterol, diabetes and body
mass index (BMI)). Meta-analyse (4)confirms that cardio-respiratory
fitness is a very valuable indicator of cardiac and all-cause mortality
risk, equivalent at least to the traditional risk factors. Muscular
strength is an independent positive factor.(5)
Professors Hingorani and Hemmingway (6) have elegantly reviewed the
debate about balancing the individual and population benefits of statins
for preventing cardiovascular disease. The Cochrane systematic review on
statins (7) gives a more detailed perspective, suggesting few benefits of
statin therapy in primary prevention, as there has been some bias in
publishing positive results and a failure to report adverse events.
In public health the debate about lowering cardiac risk in the
general population in those at low as well as high risk should now include
the assessment of cardiorespiratory fitness. A public health campaign to
improve fitness would have many benefits including improvement in cardiac
and all-cause mortality risk factors. In an ageing population, the
advantage of improving fitness levels will be the benefit of maintaining
elderly people's independence without the side effects of statins (8)
which have been well documented. Prescribing exercise and strength
regimes should be routine and may cost very little or nothing at all.
1) Wildgust HJ, Beary M. Are there modifiable risk factors which will
reduce the excess mortality in schizophrenia? J Psychopharmacology 2010;
2) Global health risks: mortality and burden of disease attributable
to selected major risks. WHO press, World Health Organization 2009; ISBN
978 92 4 156387 1.
3) Blair SN. Physical inactivity: the biggest public health problem
of the 21st century. Br. J. Sports Med. 2009; 43: 1-2.
4) Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Asumi M et al.
Cardiorespiratory fitness as a quantitative predictor of all-cause
mortality and cardiovascular events in healthy men and women: a meta-
analysis. JAMA 2009; 301(19):2024-35.
5) Ruiz JR, Sui X, Lobelo F, Morrow JR, Jackson AW, Sj?str?m M et al.
Association between muscular strength and mortality in men: prospective
cohort study. BMJ 2008; 337(7661): 92-95.
6) Hingorani AD, Hemingway H. How should we balance individual and
population benefits of statins for preventing cardiovascular disease? BMJ
7) Taylor F, Ward K, Moore THM, Burke M, Davey Smith G, Casas JP,
Ebrahim S. Statins for the primary prevention of cardiovascular disease.
Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD004816
Source: Cochrane Library
8) Hippisley-Cox J, Coupland C. Unintended effects of statins in men
and women in England and Wales: population based cohort study using the
QResearch database. BMJ. 2010; 340: c2197.
Competing interests: No competing interests