What statins tell us about the mess in evidence based medicine

June 30th, 2014 by Ben Goldacre in evidence | 19 Comments »

Sorry to be absent, I’ve about a zillion big things shortly coming to fruition, at which point expect a deluge.

Everyone is having kittens about statins and the BMJ at the moment. Here’s what I wrote as a rabid response on the latest BMJ editorial about it, and a disco soundtrack to keep your attention focused:

www.bmj.com/content/348/bmj.g3306/rr/759401

Statins are a mess: we need better data, and shared decision making

I have two observations to make on the statin wars.

Firstly: if there is any uncertainty at all about the risks and benefits of statins – and there is – then we have failed to competently implement the most basic principles of evidence based medicine. Statins are the single most commonly prescribed class of treatment in the developed world, taken by tens if not hundreds of millions of patients every day. That would be more than enough clinical experience to resolve any research questions, if we were competently identifying all outstanding uncertainties, and conducting well-designed trials to answer those questions in routine clinical care [1]. We need better data; better dissemination of that data; and better communication of that data, in ways that help people make decisions which reflect their wishes. Statins should be the crowning glory of evidence based medicine, our perfection incarnate: instead, they are a mess.

Secondly: while disputes over individual numbers are important, the leading protagonists in the statin wars seem, above all, to be suffering under a grand delusion that all patients think like they do. On the one hand, we have clinicians and researchers insisting that no sane patient would refuse a safe simple treatment that reduces their chances of a heart attack by one in 200; on the other, we have clinicians and researchers insisting that one in 200 is a laughable and trivial benefit, which no sensible patient could ever care about.

In reality, all patients are different, and we all – as doctors or as patients – weigh up different factors differently. Some want longevity at any cost; some think taking a pill every day is an affront to their independence. Some think aching muscles are a trivial niggle; some think that side effects – even when mild, well-documented, and carefully discussed – are proof that their doctor is a reckless idiot.

When we offer statins, or any preventive treatment, we are practicing a new kind of medicine, very different to the doctor treating a head injury in A&E. We are less like doctors, and more like a life insurance sales team: offering occasional benefits, many years from now, in exchange for small ongoing costs. Patients differ in what they want to pay now, in side effects or inconvenience, and how much they care about abstract future benefits. Crucially, the benefits and disadvantages are so closely balanced that these individual differences in preference really matter.

Because of that, this new kind of medicine needs perfect information. We need clean, clear data showing the risks and benefits of preventive treatments, on real world outcomes, beyond any reasonable doubt, at every level of risk, and for as many subgroups as possible. We need shared decision making products that are universally available, carefully validated, and seamlessly integrated into routine clinical care, to help all patients make their own truly informed decisions. Lastly, we need to recognise that different patients have different priorities: different to each other and, sometimes, very different to our own.

Ben Goldacre
Research Fellow in Epidemiology
London School of Hygiene and Tropical Medicine
ben.goldacre@lshtm.ac.uk

[1] Staa T-P, Goldacre B, Gulliford M, et al. Pragmatic randomised trials using routine electronic health records: putting them to the test. BMJ. 2012;344(feb07 1):e55-e55. doi:10.1136/bmj.e55.

I might expand this with a colleague for a longer piece.

Also, I’m thinking of rattling out a very quick 90 page book on statins: they are the single most commonly prescribed treatment in the entirety of the developed world. If we fail on statins, then documenting those shortcomings is the roadmap to perfection, and getting 100 million patients involved in that discussion is one way to jolt two of my professions (academia and medicine) out of our complacency.

Lastly, we have an interesting new trial in the pipeline in this area, on which more shortly.


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19 Responses



  1. Graham said,

    July 1, 2014 at 3:09 pm

    Over the past 2 1/2 years I have been on 3 different statins. Simvastin and Pravastatin both gave me muscle pain in my legs. Atorvastatin seems to be playing hell with my balance & exacerbating the mild tinnitus I have suffered since having a stroke back in 2012.

    What I need to know is what this 1 in 200 figure actually means for me.

  2. muscleman said,

    July 1, 2014 at 4:10 pm

    If it’s perfection we are after we could, in a very great proportion of cases, not require statins at all by improving diet, lifestyle* and taking more proper exercise (not walking the dog).

    Statins are nothing if not an unmistakeable admission of defeat by the medical profession. Defeat in terms of getting their patients to do any of the above, let alone all of them sufficiently.

    I know, I know, I’m a freak never smoking, eating well within my constraints, being a distance runner and drinking only very moderately and only occasionally (it interferes with the running, and the gout).

    We know all this, but instead we debate a better ambulance at the bottom of the cliff, or are statins a series of ledges part way down?

    *Meaning eating three regular meals with regular bedtimes (no long weekend lie-ins after late nights) and drinking only very moderately if at all. These things matter. A chaotic lifestyle, burning the candle at both ends and drinking too much are major risk factors for Type II diabetes and of course Alzheimers in later life.

  3. SimonWaters said,

    July 1, 2014 at 11:22 pm

    I don’t think statins are an admission of defeat, you won’t win all the wars. Compliance averages 60%, and mostly that is “just take these pills”, it falls further when it is “take 2.5 hours out of your week to exercise”. Statins are just one more device they can use if appropriate.

    Similar comments would apply to other preventative interventions including exercise.

    Whilst exercise is reasonably well studied, and evidence based guideline recommend it, and recommend doctors recommend it, and even recommend how to recommend it effectively, we don’t understand the full risk/benefit of saying jogging, especially where there are complications like prior heart disease. We have ample clinical experience, but that hasn’t been turned into actionable data.

    All patients remain different, I work with support groups for Graves’ disease, and amongst the first advice to the newly diagnosed is “DON’T EXERCISE TILL YOUR DOCTOR SAYS IT IS SAFE TO DO SO”.

  4. Ben Goldacre said,

    July 1, 2014 at 11:35 pm

    With the best will in the world, muscleman’s comment feels like another example of empathy failure, and the same phenomenon that I described among doctors in my post. Not everyone is like you, not everyone will agree with your priorities and choices, not everyone will even be capable of doing so. Medicine isn’t for perfect people, or people like us, it’s for everyone.

  5. vanmorgan said,

    July 2, 2014 at 6:56 am

    Ben,

    Like many people, I’m taking a statin as prescribed. My cholesterol was high and, with the statin plus some diet and exercise (not enough but some) the path. tests are now within acceptable range. No noticeable side-effects. To me, the statin is a useful and justified medication taken with proper advice and monitoring.

    All this useful public discussion can be worrying … perhaps unnecessarily so? The message to reach the public via the general media is that there’s something wrong or bad with statins.

    But my non-professional reading is that statins have a place in treatment — but there’s a question mark over their wider distribution on a more preventative basis (as opposed to people like me who have diagnosed high cholesterol). Have I got that right?

    The makers of statins want to sell more and are pushing for doctors to prescribe them more widely. Yes, I’ve read ‘Bad Pharma’ and have a health distrust of the industry .

    Am I right in saying that the current debate is about the wider distribution of statins and the cost/benefit/downsides of doing so? But people (like me) taking them as part of a specific treatment should not worry and certainly not stop taking statins without medical advice.

    I ask this not just for myself but I’m sure many others in a similar position.

    Thanks,

    Van

  6. muscleman said,

    July 2, 2014 at 7:53 am

    Most people do not have either Graves disease or active heart disease. They are just overweight, under exercised, poorly fed and drinking too much.

    I’ve been there, slowly weaned my wife off it, got one offspring with Type II and another who saw that and got running.

    I fully understand how hard it is to go exercise when you come in tired from work, it’s dark and raining etc. My only advantage is that experience has taught me the difference in being mentally tired and physically tired. I yawn hugely while preparing for early evening runs. I’ve learned to ignore it. Oh one more, I grew up in sub tropical Auckland, NZ and learned to love running in the rain.

    Oh and haven’t I read study after study about how GPs don’t recommend exercise and compliance being poor when they do? Some years ago while in a sedentary phase I developed chronic heartburn, was good and went to the GP who gave me some pills. Absolutely no mention of losing the flab and getting fit. I took the pills, they worked but didn’t fancy needing to take a pill every day to feel normal so didn’t go back for a repeat. Instead I dug out my running shoes and hit the road. Academic research and personal experience dovetail to lead me to my conclusion. Along with all the figures on the number of people not reaching the recommended hours and intensity of exercise every week.

    I can imagine that being a GP must make you pretty cynical about humanity seeing easily avoided conditions present time and again. I have a brother in law who like me has gout, except his is so bad pus is coming from his toes. He didn’t know tomatoes and spinach and lentils were uricacious and drinks like a fish. Incurious and thinks fate is a bastard that can’t be fought. Faced with that as a GP I doubt I would bother either. Empathy enough?

    Now can we discuss the issue instead tone trolling my points?

  7. Malcolm said,

    July 2, 2014 at 10:23 am

    So how precise does the risk/harm information have to be?

    The sad truth is that on the whole RCTs collect and report adverse event information very poorly, the CONSORT extension for harms notwithstanding. But on the positive side, at least for the last decade or so, standards mandated by regulators for registration trials (e.g. phase 2 and 3) are pretty good.

    So, is the FDA analyis of say myalgia rates with rosuvastatin during registration trials good enough?
    www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-366_Crestor_Medr_P1.pdf

    Because I don’t think cheap/pragmatic trials will get you information that’s any better.

  8. David Bailey said,

    July 3, 2014 at 6:24 pm

    Ben,

    I really don’t think most patients who are put on statins are actually told that they stand a 1 in 200 chance of benefiting! I know I wasn’t, and while everything was going well, I naively interpreted my doctors enthusiasm for statins as at least a 30% reduction in risk!

    I actually wonder how many GP’s realise that 1 in 200 figure!

    Not being upfront with patients is a form of deception. Another is that awful euphemism, “muscle pains” – which suggests something you might get after a long hike! It took me 9 months after I stopped Simvastatin – taking diclofenac – to get over my muscle pains! I have also talked with people on Dr Kendrick’s site who have found their muscles never recovered!

    Is it possible that a few patients don’t get statin side effects, but report some “trivial niggles”, while others do get muscle side effects that are much more severe?

    I mean, I have talked to a number of people with similar experiences to mine, and they speak of cramps, difficulty walking, joint pains etc.

    It is actually incredibly easy to hear horror stories about statin side-effects – just ask a bunch of over-60’s!

    As you say, maybe some patients really would take statins if they were told of the 0.5% gain and the potential for nasty problems – and if they want to make that informed decision, all well and good!

  9. Ben Goldacre said,

    July 3, 2014 at 6:35 pm

    You’re mistaken. The benefit for each individual from statins depends on their preexisting cardiovascular risk. I have no idea what your cardiovascular risk is (and I don’t want to know, since I’m not your doctor) so I’ve no idea what benefit you would get, it may well be rather large.

  10. David Bailey said,

    July 3, 2014 at 8:11 pm

    Well to whom does your figure of 1 in 200 apply? I have no history of CV disease, am a life long non-smoker, aged 64, and I take tablets for hypertension. I also exercise pretty regularly.

    I don’t really want to discuss my case, I am trying to get at the general issue – no actual numbers were discussed when I was prescribed Simvastatin, and I am guessing that is typical.

    I can’t believe many people would take a pill for the rest of their lives unless it offered at least a 10% reduction in risk in their circumstances. If there really are such people, fine, but I don’t think people are given the information in such a form.

  11. David Lloyd-Jones said,

    July 6, 2014 at 12:29 pm

    Many people will find the Star Wars Disco an inadequate replacement for statins, perhaps because of the time required to put on the gold or black uniforms required by the senseitachi.

    Such people might like to consider the alternative, somewhat Canadian way of dong things, shown at taichicentral.com/all-the-tai-chi-in-the-world-cannot-prepare-you-for-some-things/

    -dlj.

  12. Joe Graedon said,

    July 6, 2014 at 8:27 pm

    Dr. Goldacre helped fan the fires of controversy when he and his colleagues suggested that the only documented side effect of statins was a slight increase in the risk of diabetes.

    Based on the randomized controlled trials it was asserted in this BMJ article that musculoskeletal complaints were no greater among people on statins than on people on placebo.

    While it is true that RCTs did not demonstrate muscle pain, weakness and other musculoskeletal complications, that is more a failure of the RCT process. The very definition of myopathy in such trails has been highly problematic and variable. That is, there is no universal definition.

    There is another problem with RCTs and that is the way such ADE reactions are collected. There is great variability in the way the data are obtained by different protocols.

    Such flaws make the conclusion that statins don’t cause side effects (especially myopathy) both contentious and misleading.

  13. peajay32 said,

    July 11, 2014 at 5:28 pm

    As someone coming under pressure from my GP to take a statin for elevated total cholesterol and LDL, I would read any book you write on statins with great interest.

    I’m doubtful of the reliability of total cholesterol and LDL as indicators of CAD risk. I’m also concerned about statin side-effects as, so it seems, these can be buried by pharma-sponsored trials and I’m hearing so much anecdotal evidence of problems.

    I wonder if your epidemiology perspective might shed light on some other important questions, too. For instance, whether statins, even if they do reduce heart disease/stroke/CAD risk as is claimed, do so by another mechanism than reducing cholesterol? And could it be that average (or even higher-than-average) cholesterol can be protective overall (so that statins, by reducing cholesterol, might actually increase the risk of other life-shortening/debilitating conditions like cancer and Alzheimer’s)?

  14. bt0558 said,

    July 28, 2014 at 8:26 pm

    Sorry to be a nuisance but I am both a teacher and a potential recipient of statins (at 56). This post is about evidence based medicine but also has implications I think for evidence based teaching.

    I have wondered how evidence from RCTs and meta analyses could be useful for me as a teacher, as my students are all different.

    In Ben’s reply (5) above he explains that….

    “The benefit for each individual from statins depends on their preexisting cardiovascular risk. I have no idea what your cardiovascular risk is (and I don’t want to know, since I’m not your doctor) so I’ve no idea what benefit you would get, it may well be rather large.”

    The implication seems to be that it is the individual that will determine whether statins are appropriate so why bother with the large scale trials etc. The large scale trials surely cannot tell us about the individual.

    I am thinking about evidenced based teaching and the issue appears to be similar. I can find out that maybe 70% of people benefit from using mindmaps, but I need to know whether mindmaps are effective for each of the people I teach. This is why Ben’s “you are mistaken” concerns me.

    Will RCTs etc also tell me which individuals will benefit or do I apply to everyone knowing that for X% it wont work, but only experience will tell me which 30%.

    I hope that makes sense.

    Does anyone have recommended reading that may illuminate for me?

  15. bt0558 said,

    July 28, 2014 at 9:50 pm

    Just found this paper by Ben…

    media.education.gov.uk/assets/files/pdf/b/ben%20goldacre%20paper.pdf

    Seems to be just what I need. Will read and inwardly digest.

  16. Joan said,

    August 10, 2014 at 9:22 am

    I found this very helpful and am sharing with friends, many if whose cardiologists want to put them on statins, even though they’re low risk according to guidelines. I’m switching cardiologists as I’m having the same problem with my previously wonderful cardiologist of 10 years. I’m low risk with a calcium score of 1 (up from 0 after 5 years) and my lipids are all within normal limits, though my HDL could be higher and more bubbly. But my cardiologist, a healthy normal weight woman who gets regular aerobic exercise, has joined her colleagues and is now on statins – the miracle fountain of youth pill. She wants to put me on statins if my LDL gets too high, even if nothing else changes. This is not good medical practice to me and the ongoing conflict has greatly reduced my trust. Unfortunately, I don’t think my experience is atypical from talking with my friends.

  17. gers said,

    September 11, 2014 at 11:53 pm

    so, when do we learn where the figure of 1 in 200 comes from? on June 30th Ben says 1/200. On July 3rd he says ” it could be rather large” . Obviously, the whole piece depends upon this single figure of risk. what is it, on average?

  18. art2science said,

    September 26, 2014 at 1:40 am

    Hang on. Both statements can be true at the same time:
    “Patients stand a 1 in 200 chance of benefiting!” and
    “statins give a 30% reduction in risk.”
    There is no conflict. This is why I think risk ratios are a poor way to present medical results to laypeople!!

    Example: You can have a big RELATIVE reduction in the risk of a RARE event, which adds up to a SMALL chance of benefitting. Suppose disease A has a 1 in 100 chance of affecting you, and suppose that if you take pill Z, it cuts this risk in half. So out of 1000 people, instead of 10 people getting A, now only 5 will. That is a 1 in 200 chance that you benefitted.
    A key point, that is often not mentioned, is that side-effects, and costs (financial, inconvenience, side effects), of a treatment have a chance of affecting everyone who gets that treatment, while the benefits can only help those people who would have had the target ailment without treatment. This leads to calculations about “cost per life saved” and so forth, but those are generally not highlighted in press articles, at least in the US. I’m glad to see the statin discussion is finally starting to address this!!

  19. Striker said,

    October 13, 2014 at 9:58 pm

    On the patient side of the fence, how can a statin patient know they have benefited from the drug in terms of avoiding a CV event or extended their lives by a single day?

    Many drugs I can think of have a verifiable benefit to the patient, but not a single statin patient can demonstrate that the drug prevented a heart attack or caused them to live one day longer. For the individual patients, their benefit is unverifiable.

    They get lower cholesterol, and trust what they are being told by the industry.