Mass treatment with statins
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4745 (Published 23 July 2014) Cite this as: BMJ 2014;349:g4745
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As a 74 year old retired doctor with a family history of heart disease, I have in the recent past been a recipient of both Simvastatin and Atorvastatin. I am amazed that so little has been made of their potential side-effects. In my own case, these were so devastating that I refused point blank to continue with their use under any circumstances (I now take Ezetimibe without any problems).
Some months after commencing treatment with statins I developed the following: 1) an intractable Achilles tendinitis sufficiently severe to make walking difficult and running impossible. 2) very severe sleep disturbance manifested by violent dreams (on several occasions I punched my wife or the bedside table, before abruptly waking, or found myself out of bed "sleep walking", and on one occasion having thrown myself out of bed altogether). 3) night cramps in my legs sufficient to make sleep temporarily impossible. While these symptoms may sound hilarious, they are in reality very frightening (and painful!).
After some considerable time it occurred to me that the statins might be the precipitating factor for my symptoms. A change from Simvastatin to Atorvastatin had no effect, however, so I stopped them completely. In two to three months the pain in my Achilles tendon gradually resolved, the nightmares became less frequent and finally resolved completely, and the night cramps disappeared.
Owing to the lengthy asymptomatic latent period before the onset of symptoms, I at first attributed them to other factors, such as the rubbing of my heel by a new pair of shoes. Not only was the onset of symptoms delayed, but their complete resolution after stopping treatment, took several months. I wonder if this may explain why the link between statins and their potential to cause serious side-effects , has been so infrequently reported.
Competing interests: No competing interests
Dear Dr Grant,
Thank you very much for taking the trouble to point out the typo on the statins report page, both in your response and via the telephone. We have now corrected the text.
Competing interests: No competing interests
Dear Fiona Godlee,
Your Independent Statins Review Panel report lists some NOT FOR PUBLICATION letters to you from Professor Sir Rory Collins, at the Nuffield Department of Population Health. Richard Doll Building, Oxford, as being from Royal Collins.1
SP17 Letter 1 from Royal Collins to FG dated 31 March Not for Publication
SP18 Letter 2 from Royal Collins to FG dated 14 April Not for Publication
SP19 Letter 3 from Royal Collins to FG 25 April
SP20 Letter 4 from Royal Collins to FG 28 April Not for Publication
Statin use has been treated with such reverence by the medical profession, I think partly as a result of flawed epidemiology, that this is a very funny Freudian slip.
In contrast, a well-researched book by James Yoseph and Dr Hannah Yoseph’, “How statin drugs really lower cholesterol and kill you one step at a time”, makes excellent if disturbing reading for doctors.2 Statins are derived from mycotoxins. Historically, toxic and/or oestrogenic mycotoxins in mouldy grain have devastated populations.3
Statins lower blood cholesterol by blocking the mevalonate pathway which also blocks cell growth and replication. The Yosephs think this is catastrophic and all that varies is how long it takes each cell to die. In all cells, mevalonate travels down the mevalonate pathway to make cholesterol and isoprenoids (including Co Enzyme Q10). These stimulate the cell to grow, replicate its DNA and divide into two cells. Mevalonate is the essence of cell renewal and life. Although statins are HMG-CoA reductase inhibitors, reductase production also can increase and LDL receptor activity increases (presumably due inherent safety feedback mechanisms).
Dr Hannah Yoseph describes how difficult it has been to work as a doctor who does not prescribe statins. The same prejudices have been met by doctors like me who do not prescribe hormones. Confusingly, although hormone use increases the main causes of death (cancer, vascular disease and mental illness and violence), prestigious studies have reported mortality rates as half of the national rates.3-6
Increases in harm and mortality from statins, hormonal contraceptives or HRT, have been grossly underestimated for decades while fundamental adverse changes in cell chemistry are ignored.
There are valid reasons against any treatment with statins.
1 The Independent Review Panel Report. BMJ 2014 August
2 James Yoseph J and Dr Hannah Yoseph. How statin drugs really lower cholesterol: and kill you one cell at a time. Amazon Paper Back 12 Mar 2012
3 Schoental R. Climatic change and human health. JR Soc Med 1994: 87:495.
4 McPherson K. Concerns about the latest NICE draft guidance on statins BMJ 2014;349:g4130.
5 Grant ECG, Re Mass treatment with statins Exclusions from trials? BMJ 2014 http://www.bmj.com/content/349/bmj.g4745/rapid-responses
6 Dr Ellen Grant. The Bitter Pill. How safe is the perfect contraceptive? Hamish Hamilton, London 1985 and Corgi, Great Britain 1986 and also published in Norway, Holland, Denmark, France and Japan.
7 Dr Ellen Grant. Sexual Chemistry, Understanding the pill and HRT. Cedar, Reed Books, London, 1994
Competing interests: No competing interests
Richard Smith asks a good question: “Is prescribing statins qualitatively different from vaccinating healthy people or giving advice on diet?” My answer is yes, it is qualitatively different from vaccination, but less so from dietary manipulation. (Richard Smith believes, however, and I’m with him, that dietary advice often has a tenuous basis in reliable evidence1.)
To vaccinate someone is to give, or to simulate, an infection, knowing that in this form it will be far less risky than the infection the person is liable to encounter in nature. Information has been imparted to the memory of the immune system.
In contrast, the continuous intake of a statin is effectively the re-tuning of an enormously complicated system of feedback loops, the metabolism that maintains the “milieu interieur”. The statin places an obstruction in the mevalonate pathway, and this re-tuning of the machine is beneficial when there has already been a threatening event due to atherosclerosis, e.g. heart attack or stroke. A similar decision is sometimes made on a man-made machine that is giving trouble: it may be preferable to run it off-tune or at lower speed so it can limp home, rather than run it at the higher risk of its completely breaking down and stopping.
The question is: do you want to run a well-adapted, well-running machine that way?
1 Ioannidis J. Implausible results in nutrition research. BMJ 2013;347:f6698
Competing interests: No competing interests
Re: Mass treatment with statins - The implications of wider uptake of statins for primary prevention
The background prevalence of disease in the population is key in this argument. If an increasingly larger proportion of the entire population needs to be targeted, putting more people (they are not patients) on statins may paradoxically may be the wrong approach.
Firstly, the pre-test probability of high future cardiovascular risk will reduce the wider one casts the net as the prevalence of high-risk individuals reduces, and hence the number of false positives (individual falsely identified as having a high cardiovascular risk) will increase. Paradoxically, if one suspects that most of the population has a high pre-test probability of being at risk of future premature cardiovascular disease, then does it then follow that we should we treat and medicalise all adults? With the high absolute numbers of false positives with such an approach, the side-effects of statins may over-ride their benefits. If however most of the population is at risk of future premature cardiovascular disease, then putting statins for example in the tap water would still be unacceptable.
Arguably, this is an incorrect solution anyway, as drugs do not eliminate the underlying societal-level causes of the disease. For example, the nutrition transition in developed, and increasingly, in developing countries(2) should be dealt with by a change in food policy, not using cholesterol-lowering medication to deal with its consequences. Encouraging the whole-population uptake of healthy behaviours through changes in food and physical activity policies, especially where individual choice is not working, is preferable to the widespread taking of tablets as a population-level intervention. These strategies may be preferable rather than casting the statin net out further.
1. Wilson J, Jungner, G. Principles and Practice of Screening for Disease. WHO Chronicle 1968;22(11):473.
2. Drewnowski A, Popkin BM. The nutrition transition: new trends in the global diet. Nutr Rev. 1997 Feb;55(2):31-43.
Competing interests: No competing interests
In your Editorial “Mass treatment with statins”, published 23-july-2014, you warn TheBMJ-readers that as long as there are no randomized clinical trials on symptomatic side effects of statins you will miss vital scientific information needed for making well-informed clinical choices in your endeavors to help doctors to make better clinical decisions.
You wrote that mass preventive treatment with statins requires bigger trials and better reporting than usually. You ended your editorial with the words: “We can say only that statins are likely to do more good than harm”.
In my opinion your editorial conclusion is much too lenient, tolerant on mass treatment with statins . Now I understand why some doctors think that evidence based medicine is broken. In my opinion, EBM is not broken at all: it is in danger and a victim of under-reporting.
I blow the whistle: EBM is in danger! This is a sort S.O.S!
“Hora est” :
The time has come to counter-attack those who endanger evidence based patient oriented clinical decision making. The time has come to fight against experts who have under-reported on statins and not warned about the dangers of metal chelating agents
“Aude sapere”:
Dare to be wise. Beware of mass treatment with statins!
Statins are metal chelating agents and said to inhibit HMG-CoA-reduction and sterol biosynthesis. Statins lower cholesterol and are widely used to prevent heart disease. However, up to now there are no reliable scientific clinical trials that tested the hypothesis that statins can safely and effectively be used for prevention of heart disease. As long as that is the case statins can best be regarded as unscientific unproven alternative medicine for prevention of heart disease.
Ref. : BMJ/critical thinking/ Tjaard; BMJ/diabetes expert/Tjaard; BMJ/ Alzheimer/zinc/Tjaard; BMJ/ Tamiflu /Tjaard/ BMJ/doc2doc/Chalmers/statins/Tjaard
Competing interests: No competing interests
Ben Goldacre and Liam Smeeth argue that when doctors prescribe statins to “healthy” people they are practising “a new kind of medicine.” This seems a view that is wrong because it is narrow in time and geography.
Many kinds of traditional medicine—Chinese traditional medicine and Ayurvedic medicine—have concentrated on keeping people well rather than treating sick people. Indeed, it may be Western medicine that is unusual in concentrating on treating sick people and particularly in fending off death.
And is prescribing statins qualitatively different from vaccinating healthy people or giving advice on diet? The advice on diet is based on much flimsier evidence than that available for statins. Indeed, as John Ioannidis has shown, most nutrition research is of extremely low quality and plain wrong. (1)
It is concentrating on treating sick people that is new, and I think I’d prefer to see my taxes used more for health creation than patching up sick people, many of whom would be better off dead, a blessed, zero carbon state.
1 Ioannidis J. Implausible results in nutrition research. BMJ 2013;347:f6698
Competing interests: I have taken the polypill, which includes a statin for six years.
At the end of the article the authors say that it is not good enough only to say that statins are more likely to do good than harm. To suggest one can do better is to set an unachievable target. This is because like is not set against like, for example, in another context it is ingenious to ask whether the ready availability of good music is more important than the absence of bad architecture.
One can say that in the narrow terms of their use statins prevent far more catastrophes than they cause and therefore are for all intents and purposes are safe. One can and should endeavour to iterate towards a narrow estimate of their relative and absolute benefit in naïve low risk populations, accepting that this will always remain an approximation more likely to over-estimate the effect than the contrary. The insuperable problem is that harms are not the immediate antitheses of the benefits. The further the harm is from a clear-cut side effect in the target system, and from being consistent in incidence and impact, the truer this is. For example, muscle pains are not in the same system and their incidence and impact are inconsistent. The potential hazards of investigating the fit and the perceived harm of medicalisation of the population are even more distant difficult to assess. It will therefore never be possible to provide the evidence for, let alone, achieve a consensus on a threshold for intervention.
It may appear to be a public health conundrum but for the reasons above a universally applicable medical solution can never be found. Furthermore as the benefit of a herd approach, akin to universal immunisation, has to be set against the implications of mass medicalisation it is as much a philosophical as a medical question.
A radical change in approach is indeed needed accepting the above. Individuals must be free to make the decision for themselves, unencumbered as much as possible by the views and interests of medical and public health lobbies.
The solution is to make statins freely available without prescription or investigations at cost price for primary prevention in otherwise low risk subjects. As statins are known to be safe, the information given should concentrate on the benefits and the individuals left to find out for themselves the relevance of side effects to their own lives. If their own cost benefit analysis is positive or they are philosophically sympathetic to the herd approach, they might decide to continue treatment. As the initiative is theirs, they are saved any adverse effects of resentment of perceiving medication was being pressed upon them.
Competing interests: No competing interests
The NICE guidance recommends a primary prevention systematic strategy to identify all those at risk from CVD. Is this not the NHS Health Check programme? Why is it not referenced in the guidance? What other primary care systematic strategy should be put inplace to identify those at risk if it is not the NHS Health Check approach being developed by Public Health England ?
Competing interests: No competing interests
Re: Mass treatment with statins
"Mass precription for modest individual benefit is new".
It is not.
Mass immunisation is largely about modest individual benefit but larger population gain. Prescribing statins at the 10% ten year risk level involves numbers of healthy people that are comparable to interventions such as immunisation programmes. Society should expect the same from statins in terms of risks and benefits as they do from the immunisations their children receive.
I think the debate still has a long way to go.
Competing interests: No competing interests