Statins, Statins Everywhere

The health of America is in trouble. Life expectancy is noticeably lower than in other developed nations, 15% of the country lives precariously without health insurance, and the launch of Obamacare was so badly botched that this much-needed health reform is in serious jeopardy. Not to worry, though, the American Heart Association and the American College of Cardiology have a plan that will rescue the health of the nation: put a third of US citizens on statins – that ought to do it!

The new guidelines, released last month was widely reported in the UK press. The Mail misleadingly called the publication a new study rather than a set of guidelines, while the BBC gave a more measured view, including a revealing statistic that roughly half the expert panel had financial ties to the makers of cardiovascular drugs. What is worse, while the panel’s conflicts of interest appear to be clearly presented, with neither the chair nor co-chairs having conflicts, the superb investigative journalist Jeanne Lenzer has discovered that the chair in particular has been rather misleading with declaring his own interests. The protestation from the AHA spokesperson Dr George Mensah that ‘It is practically impossible to find a large group of outside experts in the field who have no relationships to industry’ is hard to swallow. In a country with as many specialists as the US? There were only 15 members on the panel – is it really that hard to find experts without financial ties? Or is it harder to tell some Key Opinion Leaders that their much vaunted opinions are not welcome since they are too close to industry?

The major change to the guidelines is that there is less emphasis on absolute levels of cholesterol, and a new category for treatment in those aged 40-75 with an estimated 10 year cardiovascular risk of 7.5%. Current UK guidelines recommend treatment at 20% risk, but NICE say they are looking at the same evidence as the US, before publishing new guidance next year. Despite the important debate in the medical press about overmedicalisation – spearheaded by the BMJ’s excellent Too Much Medicine series – we can expect a lowering of treatment thresholds when NICE issues its verdict.

The problem with the way we present guidelines, though, is that they are far too black and white, when the world of medicine we inhabit with our patients is generally full of grey. The question we should be asking is not what the threshold should be for treatment, but how to empower patients to make their own, informed decisions – because ultimately, the level of risk a patient is prepared to accept before they take a tablet is a personal decision, and a panel of experts has no authority to tell patients what risk they should, or should not take.

If we use the 7.5% cut-off, for instance, and assume that taking a statin for 10 years would lead to a 50% reduction in significant cardiovascular events (which is likely to be a gross over-estimate). This means that 3.75% of patients would avoid an event by taking the drug – call it 4% for ease of maths – and 96% would not benefit. The number needed to treat (nnt) is therefore 25 to avoid one event. What will our patients think about this? Surely that is entirely subjective and not for experts to dictate? One patient may have seen a close family member affected by a devastating stroke and might think any ability to reduce the risk of stroke is an opportunity to be grasped, another might consider the 3650 tablets they would have to swallow over 10 years and wonder if a 1 in 25 risk is really worth trying to avoid. In reality, the benefits of statins are much smaller than a 50% reduction, and so the nnt for low risk patients is likely to be 50, 100 or even higher.

We need a different approach to guidelines, one based on nnt, and the corresponding number needed to harm (nnh) (like this excellent calculator from ClinRisk Ltd. There should be a lower level below which the NHS says treatment is not justified on the grounds of either harm or rationing, and then a range of nnt and nnh based on individual risk. Expert panels should analyse the evidence to provide these figures, not to tell people what to do, and doctors and their patients can be given the freedom and flexibility of a large area of grey,  in which they can personalise treatment and truly empower patient choice. The experts and policy-makers won’t like it though – because it involves trusting patients, and we’ve never quite mastered how to do that.

This article was originally published in Pulse magazine (free registration required)

To wind the clock back?

I had to smile when I heard the news report on the latest research to be published in the area of dementia. It was not the research that caused my amusement – it was an important piece of work which will help to fill the gap in the evidence regarding the use of drugs such as Aricept in the treatment of severe dementia. Up until now the focus of research has been in mild to moderate disease, and the NICE guidelines reflect this by only giving approval for these drugs in the early stages of the disease. The research demonstrated, not surprisingly, that the drugs do not stop working as a sufferer moves from moderate to severe dementia, and that they effectively turn the clock back by an average of 3-4 months.

What made me smile to myself was the implication in the news that what the guidelines say must be what happens in practice, ergo thousands of patients must be being deprived of these drugs once they get to the advanced stages of the disease. In reality, while it may be easy to define the different stages of this tragic disease in a research setting, or in the controlled environment of a NICE guidance panel, in clinical practice the transition is much more difficult to ascertain. The amusing picture that came to my mind was that of a dial on the patient’s forehead clicking over from moderate to severe, with a group of white-coated doctors standing around the patient’s bed, solemnly shaking their heads before striking Aricept from the drug chart with a big red pen. It’s as ludicrous as it sounds.

So how do doctors apply guidelines? Well, it depends what sort of guidelines they are. If NICE declare that a drug cannot be used at all, then they will be adhered to quite strictly. If they advise that a drug should sometimes be withheld on the grounds of patient safety, then you can expect doctors to follow this also. However, to recommend that a treatment, that is likely to be beneficial and is suiting an individual patient, should be withdrawn on cost grounds due to a lack of evidence – well that is a different matter entirely. Doctors like to give patients treatment that they think will work, and the difficulty in defining what constitutes severe dementia gives sufficient wriggle room that in practice these drugs are rarely withdrawn on the grounds of simply adhering to guidance – at least in my experience.

So this research will help to clarify the situation, and to improve the guidelines, but will make little difference to patients on the ground. If we can wind the clock back for someone with dementia, then that can make a significant difference to their lives, and we should do just that  – but there need to be two significant caveats to that principle.

The first is that these drugs do not work for everyone. If the average gain is to reverse the progress of the disease by 3-4 months, then there must be some patients who gain more than this – even six or nine months perhaps – and others who gain less. For some this will mean nothing at all. Then there are side effects. Most patients feel fine on these drugs, but some will not get on with them – and this is a challenge with a patient with dementia. They cannot easily explain how a drug makes them feel, and may be getting side effects that we don’t know about. Only this week we were chatting over lunch about patients of ours with dementia who have had their drugs withdrawn simply because they were at a stage where they refused to take them any more – and sometimes they then got significantly better!

The second, perhaps more important, caution here is that we will not always want to turn the clock back. Dementia can be an interminably slow process both for the sufferer and the family, who can only look on and see their loved one regress as every month passes. If the situation three months ago was intolerable, why would you want to go back to it? Sometimes these drugs can help to settle difficult behaviour in a person who is confused, but dementia can get to a stage even beyond that, where the patient is incapable of feeding themselves, speaking, toiletting or even sitting in a chair. When you get to that stage, there is a fair chance that, far from wanting to wind the clock back, you might actually want to turn it forwards as far as you can.