230. Statins: Expert Witness, Judge and Jury

The recent spat between the BMJ and The Lancet about statins must leave the ordinary members of the public in a complete state of confusion. If the leaders of the medical professions cannot agree, what chance is there for the non-specialist?

Essentially the key issue is the costs/benefit equation, which relate to the advantages and the side-effects.

In order to assess these, trials are conducted in which similar groups are compared. One is treated with the drug being studied and the other is given a placebo. The vast majority of these are funded by the drug companies themselves.

Pro-statin

The pro-statin position was presented in an article in The Lancet, which was prepared by the Cholesterol Treatment Trialists’ (CTT) Collaboration at the University of Oxford headed by Professor Sir Rory Collins (1). The key points made include the following:

Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term;
The only serious adverse events that have been shown to be caused by long-term statin therapy—ie, adverse effects of the statin—are myopathy, new-onset diabetes mellitus, and, probably, haemorrhagic stroke.

It concludes that the benefits greatly outweigh the incidence of adverse side effects and hence:

“It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events.”

In an editorial in the same issue the editor, Dr. Richard Horton stated bluntly:

“Controversy over the safety and efficacy of statins has harmed the health of potentially thousands of people in the UK(2)”.

Clearly The Lancet has come down firmly in favour of statins.

The doubts

On the other hand the BMJ is not convinced. The editor-in-chief, Dr. Fiona Godlee has written to the Chief Medical Officer, Dr. Sally Davies, requesting an independent review into the use of statins(3). In an article Dr. Harlan Krumholz makes the following points:

There is little consideration of the limitations of the trial evidence;
The trial populations do not fully reflect the diversity of patients seen in contemporary practice across the world;
Few trials have included people over 80 years old, a growing population that has an increased susceptibility to adverse drug effects;
The individual trials were also underpowered to detect many relevant harms;
The timing of the trials is a matter of concern because, even without statins, the experience of patients with cardiovascular disease even a decade ago is much different from that today (4).

Those who have taken in interest this topic will know that Sir Rory Collins is a very keen advocate of statins. Three years he complained about a paper in the BMJ, which had stated that 18-20% of those on statins suffered side-effects and demanded that it should be retracted. It was accepted that the figure quoted was too high and a correction was issued. Despite this he continued to make protestations and as a result the BMJ established an independent group to conduct an assessment.

The panel unanimously rejected retraction and also noted with concern the failure of Collins to respond to offers from the BMJ to express his views in an article. On the other hand he did give an interview to The Guardian in which he criticised the way the BMJ had handled his complaint (5).

On another occasion he told The Guardian that the bad publicity about statins is:

“.. is a serious disservice to British and international medicine.”

He claimed that it was probably killing more people than had been harmed as a result of the paper on the MMR vaccine by Andrew Wakefield.

“I would think the papers on statins are far worse in terms of the harm they have done.”(6).

It is also relevant to note that one of the authors involved, commented that Collins had not disputed his conclusion that CTT data failed to show that statin therapy had not resulted in any reduction in mortality over 10 years in those who had <20% risk of heart disease.

This investigation also revealed that the CTT had received very substantial funding from drug companies over the past 20 years, which amounted to about £1 Million per month in today’s terms.

Making sense of it all

It is impossible to discount the financial aspects related to this issue. Even for a pharmaceutical company, there is big money going to the CTT. As a business, it is buying not only expertise but also the prestige, which goes with the University of Oxford and a high-flying academic, who is a Knight of the Realm and Fellow of the Royal Society (FRS). The last thing that the company wants or expects is any suggestion that there are problems with any of its products. Similarly the recipients of the money will be only too well aware of the company expectations. There is ample evidence to show that the interpretation of research is strongly influenced by the source of funding. So we should not be surprised in the least that the Oxford academics are using every trick in the book to maintain and defend their stance. Effectively they are acting as expert witnesses. The fundamental weakness is that the opposing point of view representing the interests of the public (including patients) simply does not exist. Those who are acting on behalf of the drug industry are regarded as the independent arbiters (ie judge and jury). As things stand at present, the system is heavily biased in favour of the drug companies, which is clearly working to their advantage. If we are to make any progress, then it is imperative to understand that the current procedures are fundamentally flawed and cannot provide independent objective evaluations of drug therapies.

The patient perspective

My own view is quite unequivocal. I would never agree to have statins. Here are my reasons. As I do not have any history of heart disease and there is no reliable evidence, which proves that statins are effective for primary prevention, there is simply no justification for the treatment. Although many people are persuaded because their cholesterol levels are regarded as “high” and therefore have an increased risk of heart disease, this argument is bogus. It is true that there is an association between the incidence of heart disease and the blood cholesterol level for middle-aged men, but this does not demonstrate “cause and effect”. Furthermore the key issue is not death from heart disease but all-cause mortality (ACM). We now know that for people in their 60s and over, which is when most deaths occur, those who comply with the cholesterol guidelines have the HIGHEST ACM! (7). So there is no need to be concerned about a high cholesterol value. For women, those with the highest cholesterol have the greatest life expectancy.

For those who have heart disease, I fully accept that there can be some benefit in terms of “lives saved”. But what exactly does this mean because you will die eventually? What we really need to know is how long has life been extended. Unfortunately it is not very much. In people at high risk (de?ned as those with a 5-year risk of major vascular events higher than 25%), the average delay of a major cardiovascular event has been calculated at 0·09 years (33 days) over 5 years with a statin induced 1·1 mmol/L reduction in LDL cholesterol (8).

Against this, we have to balance the adverse side-effects. There is considerable disagreement about the frequency and severity of these. There is absolutely no doubt they do happen. While many of these may be relatively mild, in some cases they can be absolutely debilitating. There are numerous case histories of individuals whose lives have been devastated by the effects of statin treatment. Some of these are described in this blog (9). The more severe effects include memory loss and major neurodegenerative disorders including Parkinson’s Disease and Alzheimer’s Disease.

Informed choice

In my case the crucial issue is that, even assuming the most favourable scenario, it only means a bit more time in this world. However I might have to pay a very heavy price to achieve this, which could be a very marked reduction in the quality of life. For me, it is a “no brainer” to keep off statins. The clinching argument is that if I wish to prolong my life there are other strategies I can adopt, which are pretty well free of side effects and are likely to work well. These include adjustments to diet, especially reducing the intake of sugar and refined carbohydrates coupled with regular exercise.

While I do not expect everyone to agree completely with my approach, I would strongly recommend that the medical and healthcare professions adopt a strategy of “informed choice” in which the options are spelled out clearly to the patients, who can then decide for themselves what they would prefer.

This is precisely what Dr. David Unwin is doing with patients who have obesity, Type 2 Diabetes (T2D) and fatty liver disease. They can choose between a regime based on drug therapy or lifestyle change (including diet). Almost invariably they decide against the drugs. To cap it all, the results have been remarkably successful (10).

What is needed is for NICE to endorse Dr. Unwin’s approach and extend it to many other different disease/treatments.

Maybe it is more realistic to see pigs flying high!!

References

Related Posts