303. Statins: Why it is crucial to have a comprehensive picture

How often are we told that a specific drug is wonderful and is therefore essential if a disease is to be treated successfully or to be prevented. The hard reality is that this begs an awful lot of questions and is only one minor aspect of the information that anyone considering the use of the drug should fully appreciate. I suggest that most people would be interested in the following issues:

What are the chances that the person will benefit? Most people assume that any drug will have a beneficial effect if/when the drug is taken. In fact, there are extremely few where the likelihood is 100% certain that it will work for all. It is important to understand the “Number Needed to Treat (NNT)”. This is the number of people who have to be treated for ONE to benefit. In those who have had previous heart disease the NNT website concludes that after 5 years of daily statin therapy study subjects achieved a 1.2% lower chance of death, a 2.6% lower chance of heart attack, and a 0.8% lower chance of stroke (1). Or to put it another way 19 out of 20 people who took the drugs for five years saw no effect.
The other side of the coin is that there are risks of side effects, which can be damaging to a person’s health. This is definitely true of statins, although it is very difficult to obtain reliable information on the chances that this will happen. There is no systematic and through method for the collection of this information. In reality, there are compelling reasons the official figures are only a small proportion of the total. Estimates vary between 1 and 10% of the actual values.
The reliability of the information. As most of the investigations and trials are conducted by the drug companies, there is obviously pressure for the results to show the drug in the best possible light.
The same considerations apply to the analysis of the data. Ideally the original raw data should be open to evaluation by independent specialists. This does apply to statins because requests for access to this information has been repeatedly rejected.
Finally, it is important to know if there are alternative drugs that might be just as effective but be preferable in other respects. There is a tendency to assume that new drugs are “better” than ones which have been around for a long time. It is worth bearing in mind that drugs that out of patent earn much less money for the drug companies than recent ones that are patented.

With respect to statins, the very recent article by Maryanne Demasi is excellent because it explains why there are genuine doubts about the case that is usually presented to justify the use of statins (2).

Conflicts of interest

One of the driving forces behind the use of statins is the US National Cholesterol Education Program (NCEP). In the early part of this century, NCEP revised the definition of ‘high cholesterol’ by lowering the threshold so that millions more people became ‘at risk’ and therefore eligible for statins at a stroke. This step was agreed even though there was no reliable evidence to substantiate the change. Immediately, there was a huge fuss when it was revealed that eight out of nine of the committee that devised the new guidelines had direct financial ties to the pharmaceutical companies, which produced and marketed statins. Nevertheless, the proposals were implemented.

Here in the UK, the role of the Oxford University based Cholesterol Treatment Trialists’ (CTT) Collaboration has a major influence on the attitudes and policy that is related to the use of statins. In total the university has received over £260 million in research funding from the pharmaceutical industry, most of it, from manufacturers of cholesterol-lowering drugs. The head of the CTT has been an extremely vocal advocate of the case for the widespread use of statins. For example, he has argued that that ‘everyone over 50’ should be taking a statin, regardless of their cholesterol levels.

He has also claimed, rather bizarrely, that those who have raised objections to the use of statins because of adverse side effects were “far worse” and had probably “killed more people” than “the paper on the MMR vaccine.” Subsequently it emerged that the CTT had not actually included all the side effects in their work on statins (3).

Statistical acrobatics

The plot thickens even further when the statistical analysis conducted by the CTT is subject to examination. The CTT report the statin benefits in terms of the drop of ‘1mmol/L in Low Density Lipoprotein-cholesterol (LDL-C)’. Dr David Newman has commented on this approach in his blog, which was re-published in Forbes magazine (4). In this extract a drop of 1mmol/L is roughly the same as a 40-point drop in the units commonly used in the USA.

“That’s the magic: each of the benefits reported in the paper refers to patients with a 40-point cholesterol drop. Voilá. One can immediately see why these numbers would look different than numbers from reviews that asked a more basic question: did people who took statins die less often than people taking a placebo? (The only important question.) Instead, they shifted the data so that their numbers corresponded precisely to patients whose cholesterol responded perfectly.

Patients whose cholesterol drops 40 points are different than others, and not just because their body had an ideal response to the drug. They may also be taking the drug more regularly, and more motivated. Or they may be exercising more, or eating right, and more health conscious than other patients. So it should be no surprise that this analysis comes up with different numbers than a simple comparison of statins versus placebo pills. Ultimately, then, this new information tells us little or nothing about the benefits someone might expect if they take a statin. Instead it tells us the average benefits among those who had a 40-point drop in LDL.

But LDL drop cannot be predicted. Some won’t drop at all, some will drop just a bit, and some may drop more. Therefore, the numbers here tell an interesting story about certain patients who took statins, but they have no relevance to patients and doctors considering statins. And yet, the latter group is the target of the study’s conclusions.”

…..

“Perhaps never has a statistical deception been so cleverly buried, in plain sight. The study answers this question: how much did the people who responded well to the drug benefit? This is, by definition, a circular and retrospective question: revisiting old data and re-tailoring the question to arrive at a conclusion. And to be fair they may have answered an interesting, and in some ways contributory, question. However, the authors’ conclusions imply that they answered a different, much bigger question. And that is not a true story.”

Conclusion

When we dig beneath the surface, It soon becomes clear that the picture is much more complex than most people are led to believe. Patients are often placed in a position where they feel that they have no alternative but to accept the advice to go on statins. Almost certainly their perception of the benefits is grossly exaggerated, while at the same time, the extent and damaging impact of side effects are not fully appreciated. I have lost count of the number of people I have encountered who have stopped taking statins because of the pain and discomfort they were experiencing. Personally, I have not the slightest doubt in rejecting statins. The risk/benefit calculation just does not make sense. In any case it is much more advisable to make lifestyle changes such as switching to a low carb diet and taking regular exercise.

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