Painful reflections

I awoke 5 days ago with severe lower back pain – so

severe it was very difficult to stand and nearly, but

thankfully not, impossible to go to the toilet. I had

not exerted myself excessively the day before – I had

as usual supervised but avoided actually doing any

gardening (everyone’s first question!). Paracetamol

came to the rescue reducing the pain severity but

not alleviating the residual discomfort. Slowly I

mobilised but each morning since the pain has

recurred though less intense. Self-diagnosis is a med-

ic’s inherent weakness – so I stopped the statin

expecting benefit over 5–10 days. The biggest prob-

lem has been the guilt.

Guilt (from the Anglo-Saxon ‘to pay’) is defined

as a feeling of responsibility for having done wrong

or caused harm (1). So why should I feel guilty? It is

really a reflection of our medical ethos – we are not

invincible but feel if we are not available for what-

ever reason that we are letting people down. I have

had to cancel my fully booked clinics at very short

notice, an angiogram session, a thesis viva and

important guest lecture (a good friend stood in). I

found myself apologising for it all being ‘my fault’.

As I write this the discomfort troubles me but I must

not let the International Journal of Clinical Practice

down as my editorial is due – yet it is difficult to

concentrate when constantly reminded of your own

vulnerability.

I know I am not alone in responding as if I am to

blame because I have seen many colleagues soldier

on in spite of the clear need to do the opposite. I

began to think we share a defective gene which func-

tions to deny illness or at least the priorities of ill-

ness.

The telephone and internet reduce the feeling of

being isolated. Work can carry on using emails but

should it? – is not email here a way of reducing the

guilty feeling? – ‘I am not out of touch’ – ‘I can still

make decisions’. But you know you need to check or

the build-up will be burdensome and you may miss

that one essential contact (in your mind, that is).

Better to rest, read and listen to music – that is what

we tell our patients after all (‘dream on,’ said a col-

league).

The bonus is the quietness and the chance to

watch the wildlife in the garden, yet this is tinged by

the worry of not being where or doing what you had

agreed (it is that gene, I am sure). Time away from

work for whatever reason is time to reflect. I tell my

patients ‘there is more to life than work’ as I try to

involve them in a healthy lifestyle. Perhaps I need to

talk to myself too – perhaps we all need to listen

to our own advice and attempt to follow it.

We obviously do not need to have every illness to

appreciate our patients’ suffering but being the other

side of the desk is educational. Pain is the common-

est symptom presenting for medical advice. Do we

focus more on the diagnosis rather than symptom

relief? If I did in the past I will not in the future –

painful reflections these may be but they are an

important part of my life’s learning curve.

Disclosure

Self preservation.

Graham JacksonEditor

Reference1 Boyd KM, Higgs R, Pinching AJ. The New Dictionary of Medical

Ethics. London, UK: BMJ Publishing Group, 1997.

doi: 10.1111/j.1742-1241.2007.01429.x

ED ITORIAL

Targets – who needs them? Success with statin therapies

One of the interesting things about being a preven-

tive cardiovascular physician who spends far too

much time on government-related committee busi-

ness is seeing how recommendations and practice

differ. Statins are universally acknowledged as one of

the great successes of cardiovascular therapy in the

last 25 years, yet like many drugs they are under-

prescribed and under-dosed in clinical practice (1,2).

Thus the medical profession pursues homeopathy

with predictable consequences. This attitude extends

doi: 10.1111/j.1742-1241.2007.01495.x

ED ITORIAL

Statins are

universally

acknowledged

as one of the

great

successes of

cardiovascular

therapy

ª 2007 The AuthorJournal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, August 2007, 61, 8, 1239–1250

to undermining the confidence of patients by hed-

ging about the benefits and comprehensively expand-

ing on risks so that they are more likely not to

continue the treatments (3). The popular press cat-

ches hold of these ambiguities in attitude and prea-

ches about the inadequacy of conventional therapies.

I have lost count of the number of journalists who

ring up asking for help in another toxic statin story.

In fact adherence to statin and other preventive ther-

apies improves prognosis for cardiovascular disease

and they are safer than aspirin (4).

Yet treatment needs to be implemented and virtu-

ally all health systems follow a model of diagnose,

measure, treat and check for cholesterol. The question

arises – is this too complicated to implement on a

large scale? The paper in this issue, the study by

Lindgren et al. analysing prescribing and medical

laboratory data for 1993–2003 shows that the deter-

minants of adequate statin therapy in a mixed

primary and secondary prevention population in

Sweden not treated to target are recent attendance,

diabetes and an active management strategy (5). The

targets for treatment were not particularly onerous

at a total cholesterol < 5 mmol/l and a LDL-C

< 3 mmol/l, which can be achieved with moderate-to-

low doses of the commonly prescribed statins (6).

Notable features in this study are that 87% of patients

had no change in their medication from initial ther-

apy. Of patients not achieving target at 3 months,

only 8% achieved it at 12 months. The prevalence

data is similar to that found in the Return on Expen-

diture Achieved for Lipid Therapy (REALITY) survey

of 10 European countries as well as other surveys so

confirming the likely validity of the study (7,8).

Outcomes are improving in secondary prevention.

All European countries have concentrated resources

on the easily identified and relatively small secondary

prevention population. Data from the EuroASPIRE

studies (2) shows that target attainment improved

from 14% to 41% between 1995 and 2000, which

coincides with the implementation of the results of

the Scandinavian Simvastatin Survival Study allied

with the additional supportive results from other

pravastatin trials over the next few years (9). Recent

data from the UK, where primary care receives a

financial incentive to attain the same cholesterol tar-

gets (5 and 3 mmol/l) in patients with established

coronary heart disease, suggests that 78% of patients

are receiving adequate lipid-lowering therapy (10).

The recent expiry of patent protection for simvasta-

tin and pravastatin and the wide availability of cheap

generic statins has also lifted the cloud of cost which

had bedevilled this aspect of cardiovascular preven-

tion for the last 10 years (11). Studies in secondary

prevention in 1995 showed that simple strategies

involving minimal effort work (12). The near univer-

sal uptake of the simple Heart Protection Study

strategy (40 mg simvastatin) (13) is already deliver-

ing benefits on health outcomes and will deliver

more. Why has this worked? It is simple, cheap and

satisfying as the targets are easily attained. Reducing

the targets, while medically justified (14), may reduce

confidence in the cholesterol strategy unless other

agents capable of delivering the new targets are

widely available at affordable cost.

As the survey showed diabetes is increasingly being

recognised as primarily a cardiovascular disease and

in which statin therapy delivers substantial benefits

(1). Unfortunately patients with type 2 diabetes were

only a small component (200 patients) of the 4S

study and the post hoc analyses of the larger popula-

tions in the pravastatin trials were not widely publi-

cised. It took the prespecified diabetes subgroup of

the Heart Protection Study (15) followed by the Col-

laborative AtoRvastatin Diabetes Study (CARDS)

study (16) to show that LDL-C reduction was effect-

ive in preventing events in diabetes but that meant

implementation of widespread statin therapy in this

group was delayed by 3–5 years. However, contro-

versy still remains in some areas as results were less

positive in some studies: the Anglo-Scandinavian

Coronary Outcomes diabetes subgroup (17) and the

Atorvastatin Study for Prevention of Coronary Heart

Disease End-points in Non-Insulin-Dependent

Diabetes Mellitus (ASPEN) study (18). The meta-

analysis of all patients with diabetes in the statin tri-

als by the Cholesterol Treatment Triallists’ is eagerly

awaited and is likely to reinforce the necessity to

treat LDL-C aggressively in patients with diabetes.

Unfortunately LDL-C may be in part the wrong tar-

get in type 2 diabetes as the predominance of small-

dense LDL particles in this population leads to excess

risk for any given LDL-cholesterol level. Apolipopro-

tein B100 (apoB) levels might be more appropriate as

a target for therapy in diabetes as they capture all

the risk associated with triglyceride-rich remnants as

well as LDL (19), yet no guidelines have mentioned

apoB as a target for treatment despite its known

superiority as an indicator of cardiovascular risk in

large epidemiological studies such as InterHEART

(20) and AMORIS (21). There are already hints that

the prognostic benefits of preventive therapies may

not be as great in coronary heart disease in diabetes

as expected (22). Pending resolution of these anom-

alies, an aggressive statin strategy based on cardiovas-

cular risk equivalence is justified given the disease

burden.

In primary prevention, which comprised 76% of

the Swedish study, the implementation of evidence is

even more controversial. In practice, all too many

diabetes is

increasingly

being

recognised as

primarily a

cardiovascular

disease and in

which statin

therapy

delivers

substantial

benefits

1240 Editorials

ª 2007 The AuthorJournal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, August 2007, 61, 8, 1239–1250

patients are treated on the basis of cholesterol levels

rather than cardiovascular risk. Inequalities of care

surface with bias in treatment following social class

and deprivation indices and relative under-treatment

of ethnic minorities. Moreover, targets are controver-

sial in this field (14). Statins show benefits in the

ultra-low risk populations recruited for some recent

studies. In the MEGA study, pravastatin 10–20 mg

reduced events by 33% in patients achieving a final

LDL-C of 3.31 mmol/l (23). In the patients with

calculated Framingham risk < 10% recruited to the

METEOR study, aggressive therapy with 40 mg rosu-

vastatin achieving an LDL-C of 2.02 mmol/l reduced

the progression of carotid intima media thickness –

a well accepted surrogate of atherosclerosis (24). All

health systems limit treatment to patients at higher

cardiovascular risk (20%/decade) on the basis of

number needed to treat. Some physicians already

self-medicate with a statin and aspirin and some

patients are unwilling to accept a one in five risk and

thus pressure has grown for Over-The-Counter statin

therapy (25) which if adherence is good has now

been validated by the MEGA study – at least for the

male subgroup. The Swedish study has shown that

very few patients have their statin titrated or altered

after it has been started so providing justification for

a ‘fire and forget’ strategy of prescribing an adequate

dose of statin (e.g. 40 mg simvastatin) and not both-

ering with targets. The consequent 1 mmol/l reduc-

tion will reduce cardiovascular events by 20–25% at

minimal cost (9). This approach has been adopted by

the Scottish Intercollegiate Guidelines Network (26).

Other guidelines still favour a ‘test and treat’ strat-

egy with formal measurement of lipids before and

after treatment coupled with optimisation of therapy.

Given the lack of statin titration shown in many

studies of therapy implementation it may be time to

reassess this strategy but given current protocols

many patients (30%) will fail to reach target with

40 mg simvastatin and additional therapies will be

required (27,28). One accidental consequence of the

financially orientated statin-switch strategies is that it

is driving the review of patient records and also

encouraging repeat attendance for assessment and

thus may also improve the standard of care as inad-

equate doses are recognised and titrated.

There are better prospects on the horizon. The

high tolerability of ezetimibe and the cost effective-

ness of the combination of statin-ezetimibe com-

pared with switch/titrate strategies suggests that a

simple second stage addition may be all that is

required to optimise lipid control in 90% of patients

(29). Once ezetimibe-statin is generic the ‘fire and

forget’ strategy will be very tempting to Health pay-

ment organisations. At that stage it will be simple,

safe, cheap and very effective and do away with the

need for many clinic visits and laboratory investiga-

tions. It may also do away with the need for LDL-C

targets in both primary and secondary prevention as

the vast majority of patients will achieve good lipid

control with hopefully a single tablet. At that stage

we will truly have a new ‘aspirin’ for cardiovascular

disease – three times more effective and 50 times

safer. Thereafter, we may call ‘statimibe’ the universal

panacea for cardiovascular disease in the 21st century

as aspirin is relegated to the history of the 20th cen-

tury.

Disclosures

Dr Wierzbicki is the chairman of the medical scienti-

fic & research committee of the Hyperlipidaemia

Education And Research Trust (HEART-UK) – one

of the societies involved in the Joint British Societies

guideline group. He has served on the National Insti-

tute for Health and Clinical Excellence (NICE) panel

for guideline development in familial hypercholester-

olaemia and the technology appraisal for ezetimibe.

He is a member of the South East London Cardiac

Network group. He has received honoraria for lec-

tures and advisory boards as well as travel and

research grants from AstraZeneca, Bristol-Myers

Squibb, GlaxoSmithKline, Merck KGaA, Merck,

Sharp & Dohme, Novartis, Pfizer, sanofi-aventis,

Schering-Plough, Solvay-Fournier and Takeda.

Anthony S. WierzbickiDepartment of Chemical Pathology,

St Thomas Hospital, London, UKEmail: anthony.wierzbicki@kcl.ac.uk

References1 Eliasson B, Cederholm J, Nilsson P et al. The gap between guide-

lines and reality: type 2 diabetes in a national diabetes register

1996–2003. Diabet Med 2005; 22: 1420–6.

2. Clinical reality of coronary prevention guidelines: a comparison

of EUROASPIRE I and II in nine countries. EUROASPIRE I and

II Group. European action on secondary prevention by interven-

tion to reduce events. Lancet 2001; 357: 995–1001.

3 Ravnskov U. Statins as the new aspirin. Conclusions from the

heart protection study were premature. BMJ 2002; 324: 789.

4 Bouchard MH, Dragomir A, Blais L et al. Impact of adherence to

statins on coronary artery disease in primary prevention. Br J Clin

Pharmacol 2007; in press, doi: 10.1111/j.1365-2125.2006.02828.

5 Lindgren P, Borgstrom F, Stalhammar J et al. Determinants of

cholesterol goal attainment at 12 months in patients with hyper-

cholesterolemia not at consensus goal after 3 months of treatment

with lipid-lowering drugs. Int J Clin Pract 2007; 61: 1410–14.

6 Jones PH, Davidson MH, Stein EA et al. Comparison of the effic-

acy and safety of rosuvastatin versus atorvastatin, simvastatin, and

pravastatin across doses (STELLAR* Trial). Am J Cardiol 2003;

92: 152–60.

7 Van GE, Laforest L, Alemao E et al. Lipid-modifying therapy and

attainment of cholesterol goals in Europe: the Return on Expendi-

ture Achieved for Lipid Therapy (REALITY) study. Curr Med Res

Opin 2005; 21: 1389–99.

We may call

‘statimibe’ the

universal

panacea for

cardiovascular

disease in the

21st century

Editorials 1241

ª 2007 The AuthorJournal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, August 2007, 61, 8, 1239–1250

8 Wright DJ, Grayson AD, Jackson M et al. The reality of treating

dyslipidaemia in patients with coronary heart disease: a primary

care survey. Int J Clin Pract 2003; 57: 488–91.

9 Baigent C, Keech A, Kearney PM et al. Efficacy and safety of cho-

lesterol-lowering treatment: prospective meta-analysis of data

from 90,056 participants in 14 randomised trials of statins. Lancet

2005; 366: 1267–78.

10 Department of Health. Quality Outcomes Framework data 2005/

06. The Information Centre National Health Service 2007. http://

www.ic.nhs.uk/servicesnew/qof06/view?searchterm¼quality%20

outcomes (cited 2 April 2007).

11 Moon JC, Bogle RG. How to lose a billion pounds. Int J Clin

Pract 2007; 61: 2–3.

12 Fonarow GC, Gawlinski A, Moughrabi S et al. Improved treat-

ment of coronary heart disease by implementation of a Cardiac

Hospitalization Atherosclerosis Management Program (CHAMP).

Am J Cardiol 2001; 87: 819–22.

13 MRC/BHF. Heart Protection Study of cholesterol lowering

with simvastatin in 20,536 high-risk individuals: a randomised

placebo-controlled trial. Lancet 2002; 360: 7–22.

14 Wierzbicki AS. Newer, lower, better? Lipid drugs and cardiovas-

cular disease – the continuing story. Int J Clin Pract 2007; 61:

1063–77.

15 Collins R, Armitage J, Parish S et al. MRC/BHF Heart Protection

Study of cholesterol-lowering with simvastatin in 5963 people

with diabetes: a randomised placebo-controlled trial. Lancet 2003;

361: 2005–16.

16 Colhoun HM, Betteridge DJ, Durrington PN et al. Primary

prevention of cardiovascular disease with atorvastatin in type 2

diabetes in the Collaborative Atorvastatin Diabetes Study

(CARDS): multicentre randomised placebo-controlled trial. Lancet

2004; 364: 685–96.

17 Sever PS, Poulter NR, Dahlof B et al. Reduction in cardiovascular

events with atorvastatin in 2,532 patients with type 2 diabetes:

Anglo-Scandinavian Cardiac Outcomes Trial–lipid-lowering arm

(ASCOT-LLA). Diabetes Care 2005; 28: 1151–7.

18 Knopp RH, d’Emden M, Smilde JG et al. Efficacy and safety of a-

torvastatin in the prevention of cardiovascular end points in sub-

jects with type 2 diabetes: the Atorvastatin Study for Prevention

of Coronary Heart Disease Endpoints in Non-Insulin-Dependent

Diabetes Mellitus (ASPEN). Diabetes Care 2006; 29: 1478–85.

19 Sniderman AD, Furberg CD, Keech A et al. Apolipoproteins ver-

sus lipids as indices of coronary risk and as targets for statin

treatment. Lancet 2003; 361: 777–80.

20 Yusuf S, Hawken S, Ounpuu S et al. Effect of potentially modifia-

ble risk factors associated with myocardial infarction in 52 coun-

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364: 937–52.

21 Walldius G, Jungner I, Holme I et al. High apolipoprotein B, low

apolipoprotein A-I, and improvement in the prediction of fatal

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cet 2001; 358: 2026–33.

22 Cubbon RM, Wheatcroft SB, Grant PJ et al. Temporal trends in

mortality of patients with diabetes mellitus suffering acute myo-

cardial infarction: a comparison of over 3000 patients between

1995 and 2003. Eur Heart J 2007; 28: 540–5.

23 Nakamura H, Arakawa K, Itakura H et al. Primary prevention of

cardiovascular disease with pravastatin in Japan (MEGA study):

a prospective randomised controlled trial. Lancet 2006; 368:

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24 Crouse JR III, Raichlen JS, Riley WA et al. Effect of rosuvastatin

on progression of carotid intima-media thickness in low-risk indi-

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25 Minhas R. Statins: is OTC actually OTT? Int J Clin Pract 2003;

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26 Scottish InterCollegiate Guidelines Network. Risk Estimation and

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27 Mikhailidis DP, Wierzbicki AS. Attaining United States and Euro-

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2000; 16: 205–7.

28 Garmendia F, Brown AS, Reiber I et al. Attaining United States

and European guideline LDL-cholesterol levels with simvastatin in

patients with coronary heart disease (the GOALLS study). Curr

Med Res Opin 2000; 16: 208–19.

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511–28.

doi: 10.1111/j.1742-1241.2007.01483.x

ED ITORIAL

METEOR: aiming at the stars for asymptomatic carotidartery atherosclerosis?*

Several trials have shown that chronic statin treat-

ment (9 months to 4 years) reduces progression of

carotid intima media thickness (cIMT) compared

with placebo in asymptomatic individuals with mod-

erate carotid atherosclerosis and no cardiovascular

disease (Table 1) (1–7).

Similarly, the recently published Measuring Effects

on Intima-Media Thickness: an Evaluation of Rosu-

vastatin (METEOR) study recruited asymptomatic

middle-aged adults with a 10-year Framingham Risk

Score (FRS) < 10% and evidence of subclinical caro-

tid atherosclerosis (8,9); a group that would not be

considered eligible for treatment by any set of

national guidelines. The exceptional 40 mg dose of

rosuvastatin in METEOR was purposefully selected

for maximum efficacy to evaluate whether statin

treatment might delay progression or even cause

regression of carotid atherosclerosis (8). METEOR

showed that rosuvastatin reduced progression but

The

exceptional

40 mg dose of

rosuvastatin in

METEOR was

purposefully

selected for

maximum

efficacy to

evaluate

whether statin

treatment

might delay

progression or

even cause

regression of

carotid

atherosclerosis

*As a co-author on the paper and the journal’s Section Editor for Cardiovascular

Disease Prevention, Anthony Wierzbicki deferred the editorial decision on this

paper to the Editor-in-Chief.

1242 Editorials

ª 2007 The AuthorsJournal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, August 2007, 61, 8, 1239–1250