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Should NICE lower its risk threshold for statins?

The JUPITER trial showed statins have major benefits at far lower risk levels, says Dr George Kassianos. But Dr Andrew Bamji argues the benefits of statins are marginal in low-risk groups.

The JUPITER trial showed statins have major benefits at far lower risk levels, says Dr George Kassianos. But Dr Andrew Bamji argues the benefits of statins are marginal in low-risk groups.

Yes

We all look towards NICE for advice, as do doctors abroad. But occasionally, it gets things wrong. This is what has happened with its advice on using statins.

For primary prevention, NICE advised us to put patients with a 10-year risk of CVD of more than 20% on simvastatin without aiming for an LDL target. But if a target is good enough for secondary prevention, it is good enough for patients at high risk who have not had their first event. How does NICE explain that almost half of all cardiovascular events occur in apparently healthy men and women with normal or even low levels of LDL cholesterol?

The JUPITER trial, presented at the American Heart Association meeting recently, showed that patients with LDL cholesterol below 3.4mmol/l are at considerable risk of cardiovascular events and death if their C-reactive protein is 2mg/l or more. These are medium-risk patients who will not normally receive a statin. By receiving rosuvastatin 20mg as opposed to placebo, the researchers showed the incidence of heart attacks was reduced by 54%, strokes by 48%, and rates of hospitalisation and cardiac revascularisation by 47%. Even all-cause mortality was reduced by 20%!

Just as the 4S study was a landmark study for secondary prevention, JUPITER is a landmark for primary prevention. This is because of its convincing outcomes and the fact its findings apply equally to men and women, the various ethnic groups studied, smokers and non-smokers, those with or without metabolic syndrome, and even in patients with a Framingham risk score of less than 10%. Even among patients with no other cardiovascular risk factors aside from elevated C-reactive protein, there was a significant benefit with statin therapy.

Such was the superiority of the statin over placebo the safety committee stopped the trial three years early. There was no increase in myopathy, cancer, liver and renal disorders or haemorrhagic strokes, although there was a small increase in physician-reported diabetes (270 in the statin group, 216 with placebo) - a largely unexplained phenomenon already reported in other statin trials.

NICE needs to look afresh at primary prevention. The question is not can we afford primary prevention of CVD? It is, can we afford not to?

NICE also advised us to start with simvastatin and if the target of LDL below 2mmol/l is not achieved in secondary prevention, to move to simvastatin 80mg. At the time, I thought NICE was totally detached from clinical practice. It is well known that if you use the 80mg strength of simvastatin, you increase the chance of side-effects. I do not use the top dose of any statin unless there are compelling reasons.

I could not find the evidence NICE based its advice on, other than cost.

Every day I practise medicine, I think of Louis Pasteur who said: 'When meditating over a disease, I never think of finding a remedy for it, but instead a means of preventing it.' The chance to do that in CVD is just appearing on the horizon. Let's not think of this as a utopia but as reality.

Dr George Kassianos is a GP in Bracknell, Berkshire, and fellow of the European Society of Cardiology

No

I declare a conflict of interest. I have a high cholesterol (9.2 fasting at first measurement) and have abandoned statins. They have given me severe tenosynovitis in the tibialis anterior, night cramps, myalgia, severe myopathy and fatigue. You might suggest

I am a hypochondriac but try to explain my elevated creatine kinase, which also went seriously adrift on my alternative treatment of ezetimibe and fenofibrate.

I am a rheumatologist and if a patient presents with cramps or polymyalgia rheumatica without an elevated ESR I stop the statin. I have had a lot of such patients. About half are cured by the statin's removal.

We remain uncertain as to whether the apparent cardioprotective effect of statins and other similar drugs is due to cholesterol-lowering or to some other action, such as their effect on C-reactive protein. But targets have blurred rational thought. Everyone gets put on statins. The recommended doses get higher. There is no good evidence to prove older women benefit, yet my clinics teem with 70-year-olds and older, who have statins as part of a cocktail of rheumatism-provoking drugs.

JUPITER is being pushed as evidence that NICE should bring down its risk threshold for statins, without considering whether we should be doing this blanket wise, or whether we target those with raised levels of CRP - as patients in this trial had. We know inflammatory diseases characterised by a raised CRP increase cardiovascular risk, so surely it is this that we should be looking at?

Should the seriously old, who by their very survival have proved they are the fittest, be given pills to prevent a condition they neither have nor are likely to develop? It's not as if muscle pains are the only side-effects. Dr Uffe Ravnskov, in a 2006 BMJ review1, identified a whole series of problems. Dr Ravnskov has raised important questions about the differences between relative and absolute risk, which are not understood by target-setters2.

I quote: 'Assume by treating 20,000 patients, 10 die in the treatment group and 20 in the control group. The difference between 10 and 20 is 10, and 10 is 50% of 20. You may say you have lowered relative risk of mortality by 50%. But the truth is 10 out of 10,000 is only 0.1% - the absolute risk reduction. On average, the absolute reduction of mortality risk with statins was between 1% and 2%. It was highest in trials including patients with heart disease and a trivial 0.12% in the AFCAPS/TexCAPS trial, which included only healthy individuals.

'Put another way, the chance of not dying from a heart attack over four to six years for a patient with heart disease and high cholesterol is about 92% without treatment, and increases to 93% or 94% with a statin every day.'

If the payback is a life of musculoskeletal misery, is it worth it? Would I recommend treatment I would refuse myself? Can we justify spending tens of millions on these things? If we offset the small reduction in cardiovascular risk with an increase in other illnesses, I don't think the case for increased use of statins stands up.

Dr Andrew Bamji is a consultant in rheumatology and rehabilitation at Queen Mary's Hospital, Sidcup, Kent

References

1 Ravnskov U, Rosch PJ, Sutter MC et al. Should we lower cholesterol as much as possible? BMJ 2006; 332:1330-2

2 Ravnskov U. High cholesterol is good! Book, in preparation

Should NICE lower its risk threshold for statins? yes quote

The question is not can we afford to do it, but can we afford not to?

No quote

Targets have blurred rational thought

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