Oh, that was quick

November 21st, 2009 by Ben Goldacre in bad science, big pharma, regulating research | 61 Comments »

Ben Goldacre, Saturday 21 November 2009, The Guardian

Once your medicines regulator decides it should change the side effects warnings on the patient information of a drug taken by millions of people, how long do you think it would take for that change to be implemented?

In February 2008 the Medicines and Healthcare products Regulatory Agency published Drug Safety Update, Volume 1, Issue 7. This is a boring government document which you have not read. After a review of clinical trial data, spontaneous reports of suspected adverse drug reactions, and published literature, they concluded: “product information for statins is being updated to reflect a number of different side-effects as class effects of all statins.”

Everyone likes to be informed, and many people make an informed decision to stop taking statins, because of well-documented side effects such as muscle problems. What were the MHRA going to put on the new labels? “Patients should be made aware that treatment with any statin may sometimes be associated with depression, sleep disturbances, memory loss, and sexual dysfunction.” They also planned a new warning to explain that – very rarely – statin therapy might be associated with interstitial lung disease.

Now before we go any further, we should be clear on one thing. There are lots of people out there who want to tell you that statins do more harm than good, and many of these people have vitamin pills and magic diet books to sell. Back in the real world, the evidence shows that statins are effective: they reduce your risk of having a heart attack, and your risk of death over a given time period, but they reduce these risks as a proportion of your pre-existing risk, so if you are at high risk of having a heart attack to start with, a statin is more worthwhile than if you’re only moderate risk. Although of course you still have to decide if you’re the kind of person who feels enthusiastic about taking a preventive drug every day for years on end.

And we should also remember that some of these new side effects, like many of the zillions of side effects listed on patient leaflets – often in an unhelpful and unranked barrage of information – are only weakly associated with the drug. These are warning notices, and some of them are based on circumstantial evidence, speculation, and preliminary data.

But this side effects information is made available for all drugs, because it’s strong enough to be worth sharing, because it might be useful to somebody somewhere, because it might make doctors more inclined to take a specific side effect more seriously from patients, because they might act as a focus for more detailed quantitative work, and so on.

This is not the new thalidomide, and it is not a story about how statins are a hidden killer: this is, rather, a story about how risk information is disseminated to patients and doctors, and how it can be disappeared.

Because the decision to add these new side effects to the label was made in February 2008, and they still haven’t appeared. When will they make it onto the label? Soon. Hopefully. It has taken until November 2009, and the implementation has just been announced, a full 21 months later.

Why did it take so long? The mighty Drugs and Therapeutics Bulletin was sent free to all doctors in the UK until a few years ago, when the government decided to cancel a collective subscription that kept everyone up to date. DTB have discovered, from the MHRA – the regulator of the pharmaceutical industry, which is funded by the pharmaceutical industry – that implementing these changes in the statins’ drug leaflets was delayed for one reason: “one of the innovator MA [marketing authorisation] Holders was not in agreement with this wording.”

So a drug company has been able to delay the inclusion of safety warnings on a drug prescribed to 4 million people, for 21 months, because they didn’t agree with the wording. There is no conceivable world in which this is a good thing.


++++++++++++++++++++++++++++++++++++++++++
If you like what I do, and you want me to do more, you can: buy my books Bad Science and Bad Pharma, give them to your friends, put them on your reading list, employ me to do a talk, or tweet this article to your friends. Thanks! ++++++++++++++++++++++++++++++++++++++++++

61 Responses



  1. Dr Jim said,

    November 21, 2009 at 12:40 am

    I would be surprised at yet another example of perverse and arbitrary administrative pedantry costing the suffering of many, but then we’ve all just been reminded of the fact that at 5:10 am on 11th November 1918 it was known the war was over. Truth was, it was known long before this, but the real perversity was that at 5:10 am the respective sides knew it would be over at exactly 11 am.

    What hell those 5 hrs 50 mins, lives wasted for a cordial and respectable time in the morning.

  2. iamjohn said,

    November 21, 2009 at 1:21 am

    I hope you have the next piece ready Ben, because when the side effects are updated I suspect there might be some of that “hidden killer” you hint at in the media. Mind you, that could be a while because I’ve heard rumours that the board haven’t yet agreed on the new label’s colour scheme.

  3. Jerry said,

    November 21, 2009 at 1:23 am

    oh great, fuel for the big pharma conspiracy :-/

  4. jdc said,

    November 21, 2009 at 2:19 am

    Oh, good – I’ve found an excuse to comment on nutritionism:

    There are lots of people out there who want to tell you that statins do more harm than good, and many of these people have vitamin pills and magic diet books to sell.

    This could have several costs: people in a high-risk group who might otherwise choose to take statins could change their mind based on claims that statins do more harm than good; if there is no good evidence that the vitamin pills or diets in question are useful, then their promotion adds to the sum of bullshit that exists [Frankfurt wrote that “One of the most salient features of our culture is that there is so much bullshit. Everyone knows this. Each of us contributes his share.” It strikes me that some may be contributing more than their share.]; there is even a possibility that the vitamin pills and diets mentioned may have adverse effects.

  5. CoralBloom said,

    November 21, 2009 at 2:41 am

    So putting a little information on a leaflet is now as difficult as getting the UN to do anything. Consensus building! Bah humbug…

  6. hjl said,

    November 21, 2009 at 12:14 pm

    As a trainee-studenty paramedical type I kind of rely on medicines information leaflets and online MHRA info on my phone (happily not provided by my Trust) when coming accross new medications/ medications with which I’m not massively familar. Thanks for pointing out that I still need to be sceptical with these.

    And hospital doctors even though no longer getting free DTB are at least doing better than ambulance trusts, in that they actually have access to BNF and/or MIMS. I have the regular privilege of buying my own.

    Out of interest – where *should* I be looking for reliable/ believable/ vaguely current medicines information when at work?

  7. PolymerasePete said,

    November 21, 2009 at 5:22 pm

    “…this is, rather, a story about how risk information is disseminated to patients and doctors, and how it can be disappeared.”

    Not really disappeared Ben – these side effects are included in the current BNF* (September 2009)

    “Other side-effects include sleep disturbance, headache, dizziness, depression, paraesthesia, asthenia, peripheral neuropathy, amnesia, fatigue, sexual dysfunction… etc.”

    So, GPs have access to the information and could (if they wanted to cause alarm and guarantee non-compliance) explain all the potential side effects to their patients. Does seem a bit odd though that these recently acknowledged side-effects have found their way into the BNF but not on to the product label.

    *British National Formulary

  8. twaza said,

    November 21, 2009 at 5:22 pm

    bull’s eye
    50 points

  9. Allen Esterson said,

    November 21, 2009 at 9:08 pm

    Ben writes:
    “Back in the real world, the evidence shows that statins are effective: they reduce your risk of having a heart attack, and your risk of death over a given time period, but they reduce these risks as a proportion of your pre-existing risk.”

    There seems to be evidence that the benefits for older people who have not had a heart attack or stroke are marginal, and that overall mortality rate is unaffected:

    tinyurl.com/yeth4te

    tinyurl.com/y9h7ffc

    Any experts on hand to comment?

  10. skyesteve said,

    November 22, 2009 at 11:41 am

    Things come and go in medicine. Warfarin has been in and out of fashion about three times in my 20 professional years (it’s very much “in” at present judging by the number of patients coming up for INR checks every week!).
    Beta blocker were once top dog but are now way down the list of anti-hypertensives. They definitely have a role in coronary artery disease but I’m increasingly convinced they’re not what they were cracked up to be otherwise. I have numerous “case studies” of peopele who have come off them and felt transformed by the resolution of their fatigue. Anecdote I know so probably no place for it here.
    But it brings me to statins. We used to get into trouble from our local health authority because our statin prescribing was more than twice the local and national average. But now everyone else has caught up. Most people don’t get side effects though some do – inevitable given the sheer number of folks on them. In addition, the number of heart attacks and strokes in our practice has plummeted in the last 10 years since we started using statins on a widespread basis.
    But I think it is fair to say that in older people with low risks the benefits are marginal. And that’s the point. Prescribing of a statin for primary prevention should be on the basis of calculated cardiovascular risk.
    But in secondary prevention – those with heart disease, ischaemic strokes or diabetes – the evidence of benefit does seem convincing (see guidelines of SIGN or NICE or reviews in Cochrane or Bandolier)

  11. Apothecalypse said,

    November 22, 2009 at 6:51 pm

    I’m approaching 40, but if I had to go on a statin, I think I might just tell the person proposing this to poke it. Either that or it’s pravastatin or see you later, mate. No member of my family has ever had a cardiovascular incident of any description and it’s rare that they fail to make to within striking distance of their 90th birthday. However, given the burgeoning methotrexate habit that my clapped-out skeleton has handed to me, I reckon statin toxicity is the least of my worries!

    Until we actually find out which company dragged their feet and why, we may be wise to hang on before hanging them: they may yet have a valid viewpoint. All these adverse effects are more common in the treatment population anyway, and I imagine this was a right nightmare to prove or disprove. Each drug will probably have a different propensity for each, there will be some confounding comorbidities… I’m just glad I wasn’t the one collating the data. Even so, I note from the above that these adverse effects are in the current BNF (and that there’s a comment on the Guardian to the effect that you can find three of the four in some of the 2000 data sheets). Doesn’t look like a cover-up in at least two cases (Lipitor and Zocor – no surprise that these were the most popular, hence the most data). I can think of one statin that was marketed at a much later date, is rather pricey and hence little used. Could its manufacturer genuinely struggle to get sufficient data? The problem here is that I doubt that anyone will ever know, and that’s every bit as bad as the event in the first place. Even so, the MHRA could have added a caveat omitting the foot-dragger, whilst recording that they were doing so on the grounds of a lack of data.

    I also note the comment about access to the Drug & Therapeutics Bulletin. I think our author needs a small rebuke as this isn’t the whole story. NHS workers can still access the DTB free via their Athens login, just as I did to read the article on statins myself. See top right-hand quarter of page: dtb.bmj.com/

    Anyone who hasn’t, get your password from www.library.nhs.uk

    And if you saw my work bag, or study / “den” / lair of evil and twisted genius, you’d quickly understand why I’m getting a marked preference for electronic sources I can trust.

    (I’m a bit annoyed that the Guardian article didn’t cite DTB, but was out of the writer’s hands?)

    @ hjl:
    Out of interest – where *should* I be looking for reliable/ believable/ vaguely current medicines information when at work?

    Suggestion – I have a netbook and internet dongle for websites. However, this might be a result of the fact that I’m a technology geek :)

    With new drugs you have to expect that there’s going to be things added to the data sheet post-marketing. The electronic medicines compendium is free and hard copy (to which several healthcare groups are entitled free) is published once a year. If you’re not in a “free” group, find a mate who is and doesn’t use it, then get them to request theirs and nick it :) Bit big though.

    Get friendly with your local pharmacies, you’ll eventually find one with a recent BNF going free if they know you. Take their phone number too while you’re at it – then phone in and get them to look it up :)

    MIMS? I thought you said you were after a reference text, not a magazine!!

    Now in my opinion the real story that needed covering from that issue of the DTP was the aspirin 75mg one. I hope you can find a way to do that one as loud as you like without frightening off the target group.

    Right! Cheers for helping me avoid work again, nearly time for James May :)

  12. the rim groper said,

    November 23, 2009 at 2:15 am

    BG: Now before we go any further, we should be clear on one thing. There are lots of people out there who want to tell you that statins do more harm than good, and many of these people have vitamin pills and magic diet books to sell.

    TRG: I don’t have anything to sell to you or anyone else.

    BG: Back in the real world, the evidence shows that statins are effective:

    TRG: Nonsense! See if you can find ANY proof in the literature. Do not quote an advertorial like JUPITER but point me to the substantial & reproducible evidence for what you have stated. While you are at it, please explain the SCIENCE behind the notion that cholesterol is bad and then tell me why mortality is higher in people with low cholesterol.

    BG: but they reduce these risks as a proportion of your pre-existing risk [unquote]

    TRG: Ah, I see… you mean the relative risk rather than the absolute risk… would you care to quantify the absolute risk?

    BG: And we should also remember that some of these new side effects, like many of the zillions of side effects listed on patient leaflets – often in an unhelpful and unranked barrage of information – are only weakly associated with the drug. These are warning notices, and some of them are based on circumstantial evidence, speculation, and preliminary data.

    TRG: It is interesting to note that memory loss has been cited for many years as a side effect of statins and only now are the patients being warned, 20 years after the introduction of the drug group. The age group that usually gets statin therapy foisted upon them are easy to dismiss as succumbing to age-related lapses and aches and pains.

    BG: This is not the new thalidomide, and it is not a story about how statins are a hidden killer:

    TRG: Do you know ANYTHING about how and where the statins work? Please be kind enough to explain precisely what you think the results will be through the inhibition of the biosynthesis of Ubiquinone (CoenzymeQ10), Heme A, Dolichols, Prenylated Proteins and Cholesterol?

    Why do you think that general practice is far more interested in QOF awards than it is in the well-being of the patients?

  13. skyesteve said,

    November 23, 2009 at 9:23 am

    @TRG – you are right to question, especially with something as widely used as statins. You are also entitled to your opinion re GPs and QOF but please don’t paint all GPs with the same brush. Most do the best they can for their patients and most, being generalists, have to go with the “expert” advice they are given such as:

    www.nice.org.uk/nicemedia/pdf/TA094guidance.pdf

    What else can they do?

  14. erenard said,

    November 23, 2009 at 11:40 am

    Dear Dr. Ben, talking about ‘bad science’, your link to Baigent’s meta-analysis touting mortality benefit for all [no hours of lives extended given] is like finding every Afghan to be a terrorist and thus worthy of ‘treatment’.

    You must know of the 2 meta analysis [in JAMA and JACC no less] finding zero mortality benefit [rr=1.00] and no prevention of second heart attacks in WOMEN. You must also know that there were more deaths in 4S in extremely high heart risk WOMEN on statin vs. placebo and you must know that the massive HPS[tudy] also found no mortality benefit in WOMEN [p=0.08].

    I could go on but unless WOMEN don’t read your well meant writings, they are no beneficiaries of ‘treatment’.

    Finally, your Baigent meta-analysis finds benefit in heart attacks but what if, just if, that is caused by the nitroglycerin imitating property all statins share: a little less chest PAIN … and thus fewer heart attacks recorded in studies, thus fewer interventions performed but no lives saved, evidently. Take any pain killer and you’ll find less ‘need for’ knee operations but no knee structure improved.

    Baigent’s ‘need for’ revascularizations [ballooning] is of little patient worth: only 1 in 20 may have a true ‘need’ [for extremely severe angina relief or when they screw up the bypass operation]. The balance of PCI ballooning / stenting is based on ‘medical judgment’ [and financing the cathlab] but at least 4 large studies show that no heart attacks are prevented by ‘going in’, or lives saved for that matter in anyone.

    THAT is worth writing about in a next BadScience article, I propose. Baigent is BAD SCIENCE par excellence. And, P.S., while he reports benefit in generic [mainly clotting] strokes, he forgets the shown increase in bleeding strokes on statins, the worst kind [think: HPS and SPARCL].

  15. erenard said,

    November 23, 2009 at 1:49 pm

    Correction: I meant to say ‘bypass operation’ when they screw up the balloon intervention, i.e. it becomes a needed ‘rescue bypass revascularization’.

    In support of Rim Groper, indeed low cholesterol folk die first. This was comfirmed by a massive Austrian population study, and that only did not reach statistical significance in men under the age of 50. I women over that age, risk of earlier death when in the lowest 25% for cholesterol was equal to the risk of smoking: www.ncbi.nlm.nih.gov/pubmed/15006277?dopt=Abstract

    I quote: “In men, across the entire age range, although of borderline significance under the age of 50, and in women from the age of 50 onward only, low cholesterol was significantly associated with ALL-CAUSE [caps by me] mortality, showing significant associations with death through cancer, liver diseases, and mental diseases.

    For balance: “The role of high cholesterol in predicting death from coronary heart disease could be confirmed in men of all ages and in women under the age of 50.. Since statins slash cholesterol, how come that 80% of statins [including Lipitor] have shown not to lower mortality in anyone and 100% of them not in women?

    Ben Goldacer: there’s nothing I like better than people engaging in a discussion about ideas, and criticising mine. You’ve been challenged by 3 people above; quite a challenge. Looking forward to your response.

  16. jazz_the_cat said,

    November 23, 2009 at 4:19 pm

    There’s another twist in the statin story. A fair fraction of the people who have severe reactions – massive muscle loss etc, may actually have underlying mitochondrial diseases. (These are fairly rare in the general population, < 1/4000 or so for all kinds and even fewer for any given type. There are many reviews on this (not accessible without paying), but www.ncbi.nlm.nih.gov/pubmed/19504041 is a recent research article that should be available from pubmed)

    The truth is probably somewhat complex.

    from a 2007 lancet meta study of 61 or so individual studies (www.ncbi.nlm.nih.gov/pubmed/18061058)
    "Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures."

    They natter on a bit about the need to control blood pressure as well as lipids (mostly stuff that is out of my direct expertise (chemistry, theoretically)).

    I know in my own case, using these has made me feel better (placebo?) So now I'm more likely to die younger from a outdoors accident than most of my age cohort ;-)

  17. erenard said,

    November 23, 2009 at 4:21 pm

    @skyesteve. Thanks for that 45 page NICE link. One problem is that all 5 manufacturers submitted their spin on cost effectiveness and where ‘events’ are not clearly spelled or split out.

    The QALY’s and LYG’s are based on all kinds of wishful thinking and assumptions. Since there is mathematical certainty statins do not extend female lives, how can these 2 concepts involving ‘Life Years Gained’ be accepted as valid?

    Incidentally, Lipitor‘s flag ship study, ASCOT, ended with 2 MORE ‘cardiovascular events’ in women, so how can anyone accept the idea that women would derive ‘benefit’ from swallowing Lipitor? The NICE people do not talk Numbers Needed to Treat apart from 2x when they COMBINE endpoints, and men and women, and young and old.

    What can a GP do? Well read the studies him/her self since each time they put their signature on a script, they take full responsibility. Lipitor in women is malpractice, for example, regardless NICE guidelines.

  18. skyesteve said,

    November 23, 2009 at 4:58 pm

    @erenard – I think you might have missed the hint of scepticism in my first post. You clearly have strong views here and, whilst I know we’re not allowed to discuss personal stuff, it would be good to have a better idea of where you are coming from.
    I think you are right about questioning the benefit for women. I think we are all right to carefully consider the true value (outwith those with a significant hereditary lipid disorder) of statins for primary prevention in women. That’s what I was kind of trying to say when I talked about the need for careful cardiovascular risk assessment in primary prevention. And, of course, primary prevention remains a fluid area if the recent aspirin debacle is anything to go by (as mentioned by another poster).
    I think you are right to take the results of ASCOT-LLA (lipid lowering arm) with a wee pinch of salt – the results speak for themselves (even if we ignore the gender issue) – only 138 people out of 10,000 avoided a cardio-vascular event by taking a statin.
    I think the job of a good GP is to discuss the pros and cons, address the risk of side effects, talk about the guidance and offer patients an informed choice, regardless of the therapy being offered.

  19. erenard said,

    November 23, 2009 at 6:59 pm

    @skyesteve, regardless if I am a humble janitor or Nobel Prize recipient, my ‘point of view’ does not matter, the data do and they should NOT be reviewed by [often] conflicted authors or expert panels [the opinion of which depends upon who is invited to sit on them -someone else said that]. NICE is a good example of the ‘statin treatment for all having had a CV event’ so called evidence base garbage generated! Carpet bombing!

    The event and mortality data should be presented by actuaries, the profession that can generate hard NNT’s, hours of lives saved as well as tables of INDIVIDUAL [not combined] endpoints prevented or caused, per gender and per patient group, per year of statin use. That has never been done!!!

    Why would Pfizer point attention to the fact their statin [mankind’s most profitable drug ever] has never saved anyone in a clinical trial when you can cell the drug for $500-$1500/year? See their point 4.1.7 in your NICE PDF or 4.1.14: ‘The trial was not designed to examine clinical events‘ [sic].

    I am not an MD or actuary but I was recently invited to write a reality check statin review article for a cardiovascular journal. I sell, use or prescribe no drug and sell no vitamin, tee-shirt or book. Cardiovascular disease is my long-term scientific interest [I don’t particularly like pigeons, or stamps]. Dr. Ben G. and I spend similar amounts out-off-pocket on our scientific interests, BadScience and cardiovascular disease, respectively.

    If you care to post your email with {at} instead of @, I’ll send you a note. Cheers.

  20. erenard said,

    November 23, 2009 at 7:31 pm

    Let’s not forget, this exchange was triggered by Dr. Ben’s statement “statins … reduce your [that would be anyone reading this blog] … risk of death [sic] over a given time period.” [a period that would depend on one’s baseline risk, yet sooner or later.] For >/= 80% of statins, and in all women, this is unsupported by the existing statin versus placebo trials.

  21. the rim groper said,

    November 24, 2009 at 1:14 am

    @ skyesteve:
    You are serious???

    Technology appraisal 094 is an interesting document but a dreadful indictment of healthcare and the way clinicians are no longer permitted to exercise their own clinical judgement. Healthcare by fiat is all we have now. I read it when it was first published and was astonished to note that input into NICE guidance on the national policy for statin prescribing included… every major pharmaceutical company that produces a statin. Not exactly a hands off situation there – asking the drug companies to tell us what they think the NICE prescribing policy ought to be for their products. Heart UK, Cholesterol UK, the British Heart Foundation and other such front organisations for the pharmaceutical industry?

    What about the appropriately named Dr John Reckless, one time chairman of Cholesterol UK. The same person who thought we should put stains in the water supply? Please do wave TA094 in front of my face and expect me to bow before its mighty wisdom. It was a very bad sham and a shameful episode in the annals of British medical practice.

    Cardiac domain for QOF awards around 550 point last time I looked. Value then was about £66,000… a sum that most GP practices neither want nor need. At that time the average QOF payment per practice across all GP surgeries in the UK, according to DoH stats at that time was 1020 QOF points or £122,400. That piddling amount was not being left uncollected and you want to tell me that QOF awards are not motivating the GP in the UK?

    So what is a poor GP to do? The starting point is to understand how and where statins work. The next thing is to ask what is the fate of the organism when the biosynthesis that takes place within the mevalonate metabolic pathway is disrupted. Finally, I would strongly suggest that one does not permit committees of any description to think for independent practitioners insofar as clinical matters are the preserve of the clinician. How about that for an opener?

  22. erenard said,

    November 24, 2009 at 2:25 am

    NICE .. not so much. It’s much easier to understand a clinical trial than the relevance and thought patterns behind this document. Not being given the way they calculated QALYs [mixing TIA’s with fatal heart attacks] and giving ‘points’ for stable angina [something you can grow old with] when estimating risk in a “Bayesian” meta analysis. That is the kind of spooky mathematics where one calculates the risk of being hit by a golf ball even for those not playing golf. We assume risk by assigning [unreported] risk points to events.

    NICE fails to reveal those assumptions and methods.
    As said above, there is NEVER a statin mortality benefit in women and in them CHD/CVD is also a fatal disease, so what are we doing? Treating risk factors and assumed risks without saving lives.

    NICE states that statins work as well for men as for women … well not according to the huge JUPITER study where the combined endpoint NNT’s for women were DOUBLE those for men [but, oeps, no cardiovascular deaths were prevented in either gender].

    NICE spends much effort giving ranges of money values to those ‘combined but unequal weight endpoint’ QALY’s and much is above what they take as cost effective. The GP’s are then to have ‘informed discussions’ with their patients so GP’s should understand the trials and ins and outs of statins anyhow and do some independent thinking, hopefully.

  23. quasilobachevski said,

    November 24, 2009 at 6:28 am

    erenard,

    regardless if I am a humble janitor or Nobel Prize recipient, my ‘point of view’ does not matter, the data do and they should NOT be reviewed by [often] conflicted authors or expert panels

    So your context doesn’t matter, but the expert panels’ contexts do?

  24. skyesteve said,

    November 24, 2009 at 9:23 am

    @TRG – I am quite happy to be accused of failing to understand the evidence on statins or of being duped by “bigpharma” and committees BUT I must contest the implication that GPs prescribe statins to make money from QOF.
    For the benefit of others on this forum – QOF – the Quality and Outcomes Framework – is, of course, only one way in which practices earn money under the new contract of 2004 (and don’t let me get me started on that). It accounts for perhaps around 15% of practice earnings. It consists of a number of clinical and organisational domains each of which is broken down into a number of indicators for which points are awarded. Each “point” earns the practice £110.
    NONE of the indicators mention statins at all and only 3 (one in the coronary heart disease domain, one in the stroke domain and one in the diabetes domain) set targets for cholesterol. In total these three indicators amount to 28 points (that’s less than the 30 points for recording people’s smoking status). In money terms that equates to around £3000 (or about 0.3% of an average 5000 patient practice turnover) which, after tax, is worth about £1800 such that even if statins were the only way to achieve the cholesterol targets it’s hardly the reason that GPs prescribe them.

  25. erenard said,

    November 24, 2009 at 10:25 am

    Any janitor knows that if something does not clean the floor, the stuff don’t work. Anybody looking at female mortality vs placebo randomized trials knows the stuff does not add minutes to a woman’s life in the top killing disease CVD in women. It does not take an Einstein to figure that out. Here, context does not matter.

    NICE’s context [method] is assigning risk scores to OR considering TIA [mini-strokes, lasting minutes and the effects, by definition, are over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their physical context is inviting ALL statin manufacturers to comment and influence and have one of its employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

  26. erenard said,

    November 24, 2009 at 10:29 am

    Any janitor knows that if something does not clean the floor, the stuff don’t work. Anybody looking at female mortality vs placebo in randomized trials knows the stuff does not add minutes to a woman’s life in the top killing disease CVD in women. It does not take an Einstein to figure that out. Here, context does not matter.

    NICE’s context [method] is assigning risk scores to OR considering TIA [mini-strokes, lasting minutes and the effects, by definition, are over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their physical context is inviting ALL statin manufacturers to comment and influence and have one of its employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

  27. julie oakley said,

    November 24, 2009 at 11:43 am

    Come on, can someone else who demonstrably knows what they’re talking about deal with Erenard’s points. I am a scientifically uneducated WOMAN and I’d like to hear whether other credible people concur with Erenard. He/she seems to be making some valid points, but what would I know I’m only a bleedin’ artist.

  28. erenard said,

    November 24, 2009 at 12:14 pm

    Any janitor knows that if something does not clean the floor, the stuff don’t work. Anybody looking at female mortality vs placebo randomized trials knows the stuff does not add minutes to a woman’s life in the top killing disease CVD in women. It does not take an Einstein to figure that out. Here, context does not matter.

    NICE’s context [method] is assigning risk scores to OR considering TIA [mini-strokes, lasting minutes and the effects, by definition, are over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their physical context is inviting ALL statin manufacturers to comment and influence and have one of its employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

    To Julie O.: WOMEN should be upset! Here's a 2004 JAMA review about statins not saving their lives:
    www.ncbi.nlm.nih.gov/pubmed/15138247?dopt=Abstract
    Quoting: "CONCLUSIONS: For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may [like: the sky MAY fall] reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.

    Also: “Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). RR = relative risk between statin and placebo pills.

    The Authorities may answer: ‘well the studies were underpowered’. Really? 20,000 women in randomized trials and no effect on mortality! How many more women does it take?

  29. erenard said,

    November 24, 2009 at 12:44 pm

    Any janitor knows that if something does not clean the floor, the stuff don’t work. Anybody looking at female mortality in randomized trials knows the stuff does not add minutes to a woman’s life in the top killing disease CVD in women. It does not take an Einstein to figure that out. Here, context does not matter.

    NICE’s context [method] is assigning ‘risk scores to OR considering TIA [mini-strokes, lasting minutes and the effects, by definition, are over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their physical context is inviting ALL statin manufacturers to comment and influence and have one of its employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

    To Julie O.: WOMEN should be upset! Here's a 2004 JAMA review about statins not saving their lives:
    www.ncbi.nlm.nih.gov/pubmed/15138247?dopt=Abstract
    Quoting: "CONCLUSIONS: For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may [like: the sky MAY fall] reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.

    Also: “Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). RR = relative risk between statin and placebo pills.

    The Authorities may answer: ‘well the studies were underpowered’. Really? 20,000 women for years in randomized trials and no effect on mortality! How many more women does it take?

  30. erenard said,

    November 24, 2009 at 12:47 pm

    Any janitor knows that if something does not clean the floor, the stuff don’t work. Anybody looking at female mortality in randomized trials knows the stuff does not add minutes to a woman’s life in the top killing disease CVD in women. It does not take an Einstein to figure that out. Here, context does not matter.

    NICE’s context [method] is assigning ‘risk scores’ to OR considering TIA [mini-strokes, lasting minutes and the effects, by definition, are over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their context is inviting ALL statin manufacturers to comment and influence and have one of its employees, Dr. Gibbs, on the Appraisal Committee.

    That, my friend, is BadScience and a bad context.

    To Julie O.: WOMEN should be upset! Here's a 2004 JAMA review about statins not saving their lives:
    www.ncbi.nlm.nih.gov/pubmed/15138247?dopt=Abstract
    Quoting: "CONCLUSIONS: For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may [like: the sky MAY fall] reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.

    Also: “Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). RR = relative risk between statin and placebo pills.

    The Authorities may answer: ‘well the studies were underpowered’. Really? 20,000 women for years in randomized trials and no effect on mortality! How many more women does it take?

  31. Mike Kocan said,

    November 24, 2009 at 1:01 pm

    This site has a small part helping interpretation of statin research. In whole it is one of the best articles I have read to help understand scientific method.
    skepticstoolbox.org/hall/
    Also with reference to statins Malcolm Kendrick’s book, the great cholesterol con is worth a read.

  32. ghizlane said,

    November 24, 2009 at 2:08 pm

    Thanks to Ben, I have another excuse to continue my analysis of science and politics “relationship”; if ever interested in the first part, see comment 17 of Ben’s 7th November 2009 article here.

    Among other things, Ben asks in this article for the reasons behind the delay of important medical information publication. My hypothesis is this: it has nothing to do with scientific or medical value of the information, but has everything to do with juridical procedures.

    In the domain of politics, health is not looked at in medical terms and considerations but in political ones and so has to follow all juridical and constitutional rules instead. That is why, from a logical point of view, a medical argument can not be used against such decision or, in this case, delay. In other words, a doctor is sensitive to an argument saying that such a delay is not acceptable because all the harm it is causing to numbers of patients; but a politician is more likely to be sensitive to a pressure form a more or less powerful side asking for the procedure’s acceleration or delay. Thus, according to this reasoning, this kind of situations is going to continue emerging every now and then until a solution is found and legalised. What could be such solution? I have no idea, but here are some possibilities that don’t seem “good” ways to go.

    – It is not about giving doctors the absolute power over all health related matters (patient health, public health…) in which case we would be back to some sort of cleric power of doctors over people. This is why it is a “good” thing there are laws protecting patients in case of human error while being taken care of. The vice-versa works too: the law protects doctors from patients as well (in case of law suits). This seems as a balanced relationship between doctors and patients where the law plays a equilibrant role.

    – Since politicians, as pointed above, are deaf (insensitive) to medical arguments, letting politicians alone make health related decisions doesn’t resolve anything either and could lead to damaging people’s health in short or long terms time periods. Not to mention that – in case of governments pressured by companies – the only thing that matters then, is making profit even if it is at people’s health risks.

    – Having doctors forming an independent corps with enough power to make public health related decisions doesn’t seem a way to go either because: 1) to form such a corps needs to satisfy all the juridical part to exist in the first place which would only make it another political figure with a medical mask (or logo); 2) even if it could, somehow, preserve its scientific integrity, sometimes, making a public health statement – like disclosing a health care information – could lead to more harm (like triggering mayhem in the streets).

    What could be a “good” way to go then, according to this reasoning?

    Hypothetically, a “good” way to go would be finding a mean by which science (medical science here) could play a balancing role within politics (just like the one played by law in the medical field).

    Technically, how could this be applied and made possible? I have no idea.

  33. erenard said,

    November 24, 2009 at 3:25 pm

    Janitors know that if something does not clean the floor, the stuff don’t work. Anybody looking at female mortality in randomized trials knows the stuff does not add minutes to a woman’s life in their top killing disease, cardiovascular disease. It does not take an Einstein to figure that out. Context does not matter: x dead women taking statin and y taking placebo, and with x = y when you add up all the studies.

    NICE’s context [method] is assigning ‘risk scores to OR considering TIA [mini-strokes, lasting minutes and the effects, by definition, are over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their physical context is inviting ALL statin manufacturers to comment and influence and have one of its employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

    To Julie O.: WOMEN should be upset! Here's a 2004 JAMA review about statins not saving their lives:
    www.ncbi.nlm.nih.gov/pubmed/15138247?dopt=Abstract
    Quoting: "CONCLUSIONS: For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may [like: the sky MAY fall] reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.

    Also: “Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). RR = relative risk between statin and placebo pills.

    The Authorities may answer: ‘well the studies were underpowered’. Really? 20,000 women for years in randomized trials and no effect on mortality! How many more women does it take?

  34. adamk said,

    November 24, 2009 at 8:27 pm

    @erenard
    are you saying there is no evidence that statins are of benefit for women , in neither primary nor secondary prevention of cardiovascular disease?
    If that is so , why do you think the NICE guidelines suggest that they should be given to women as well as men? Do you think they are just misguided and have appraised the evidence poorly , or do you feel there are other reasons?

  35. the rim groper said,

    November 24, 2009 at 10:02 pm

    @adamk

    erenard is correct. No benefit. NICE? Ha! The much vaunted and once promising National Institute of Clinical Excellence. to think I once supported the idea of such a body. They have become a surrogate for passing on propaganda and dicta from the DoH while overseeing the adherence (N.B. you really don’t have your own clinical judgement any more) to the laid down standards.

    The same standards that were ‘suggested’ by the statin manufacturers. The same standards that are based upon a deeply flawed piece of nonsense known as The Seven Countries study, where Ancel Keys disregarded all of the countries with low heart disease and high fat diets. The same standards where dietary intake of cholesterol was found (in the Framingham study) to have “no discernible relationship” between reported diet intake and serum cholesterol levels” per the director of the study, Dr William Kannel in a press release to The News – Framingham-Natick 30/10/1970.

    The prudent clinician on the Clapaham omnibus is doing what his fellow clinicians are doing… following the (not so) NICE ‘guidelines’. What is about NICE that states that clinicians should abandon independent thought or only believe what they have been told.

    Where are the clinicians who are willing to read the literature and draw their own conclusions? Why do patients have to do what their medical practitioner tells them they must? The scenes of clinicians bullying patients, because they have cholesterol level disease, on prime-time TV, no less, is a thoroughly dispiriting scene. The harrying of people who implicitly trust the GP, only to be crippled by the toxic effects of statins, must stop now and it wont stop with people pointing to NICE and then pleading the morally bankrupt and infamous Neuremburg defence; Befehl ist Befehl.

    The clinical arena urgently needs to be divorced from pharmaceutical company largesse. You will remember the unsurprising finding of the NEJM concerning disclosure – a huge number of medics were gaining personally, from their relationship with industry. (for industry read pharmaceutical companies)

    Volume 360:325-327 January 22, 2009 Number 4
    Online Disclosure of Physician–Industry Relationships – Robert Steinbrook

    So the challenge adamk, is to practise medicine in a manner that befits the art rather than the unthinking following of orders, which at this time appear to be plainly wrong.

  36. erenard said,

    November 24, 2009 at 10:07 pm

    To quasilobachevski: Janitors know that if something does not clean the floor, the stuff does not work. Anybody looking at female mortality in randomized trials knows that statins do not add minutes to a woman’s life in their top killing disease, cardiovascular disease. It does not take an Einstein to figure that out. Context does not matter: x dead women taking statin and y taking placebo, and with x = y when you add up all the studies.

    NICE’s context [method] is assigning ‘risk scores’ to and/or considering TIA [mini-strokes, lasting minutes and the effects, by definition, are over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their physical context is inviting ALL statin manufacturers to comment and influence and have one of its employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

    To Julie O.: women SHOULD be upset! Here’s a 2004 JAMA review about statins not saving their lives:
    www.ncbi.nlm.nih.gov/pubmed/15138247?dopt=Abstract
    Quoting: “CONCLUSIONS: For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may [like: the sky MAY fall] reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.

    Also: “Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). RR = relative risk between statin and placebo pills.

    The Authorities may answer: ‘well the studies were underpowered’. Really? 20,000 women for years in randomized trials and no effect on mortality! How many more women does it take?

    To adamk Please go to the link above. What I am saying is that statins don’t extend women’s lives and that the numbers needlessly treated [NNyT] to prevent less serious events are truly massive and NICE gives no clue as to how massive. Since statins imitate nitroglycerin, they reduce angina chest pain. Since women don’t experience the typical male angina as much as men, that may just be the explanation why twice as many women needlessly are treated with statins than men to prevent non fatal events.

    Statins don’t deal with cause; they don’t add anti arrhythmic electrolytes [magnesium, potassium] or omega-3’s, and they don’t affect the strength of the artery that is determined by structural proteins.

    I don’t think most NICE panel members have anything but good in mind; they are misguided and bedazzled by the pharma herd that lives by the concept that cholesterol is evil. How do you expect a panel of these folk to counteract the spin of pharma [and Oxford U’s spin, financed by the >$m100 for statin research just from one Pharma]. Have YOU tried to understand the reasoning of NICE from the link above? Junk Science. Go to the trials and DO NOT use combined endpoints and see how well they work for women and then figure how well they may work for men. 3 new rosuva/Crestor trials: nobody saved from cardiovascular death. What can I say?

  37. quasilobachevski said,

    November 24, 2009 at 11:29 pm

    erenard and trg,

    As an interested and ignorant observer, I appreciate your passion and am interested in your comments – but there’s a certain fanaticism in your tone which makes it difficult for me to believe that you’re telling the whole story. (I suspect adamk and Julie Oakley fall into a similar category. Is that fair?)

    At the moment, I feel like I have two theories to choose from.

    Theory 1: edenard and trg are brave truth-tellers in a corrupt industry; the evidence on statins is unambiguous; NICE’s advice contradicts the evidence; therefore NICE is in incompetent and/or run by Big Pharma.

    Theory 2: edenard and trg are a little fanatical; they have cherry-picked their evidence; NICE is a controversial organization doing a controversial job; as it’s a very worthwhile job that’s always going to make lots of people unhappy, perhaps NICE should be given the benefit of the doubt.

    At the moment, I’m inclined to lean towards Theory 2, because we all know that wild accusations that such-and-such is in the pocket of big pharma are easily made but rarely tell the whole story.

    I’d love to hear any further evidence in either direction and, like julie, I’d be particularly glad to hear from any other expert sources on the science. To erenard and trg, I would reiterate adamk’s request for a more detailed analysis of NICE’s decision process. A blanket dismissal of NICE’s motives just isn’t good enough.

    (And, trg, that article in the NEJM that you link to seems to concern American health care. Surely the relationships between doctors and the pharmaceutical industry is very different in the UK?)

  38. retiredpharmaprof said,

    November 24, 2009 at 11:59 pm

    To quasilobachevski: Janitors know that if something does not clean the floor, the stuff does not work. Anybody looking at female mortality in randomized trials knows that statins do not add minutes to a woman’s life in their top killing disease, cardiovascular disease. It does not take an Einstein to figure that out. Context does not matter: x dead women taking statin and y taking placebo, and with x = y when you add up all the studies.

    NICE’s context [method] is assigning ‘risk scores’ to and/or considering TIA [mini-strokes, lasting minutes with all effects, by definition, over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their
    context is inviting ALL statin manufacturers to comment and influence with one of their employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

    To Julie O.: women SHOULD be upset! Here’s a 2004 JAMA review about statins not saving their lives:
    www.ncbi.nlm.nih.gov/pubmed/15138247?dopt=Abstract
    Quoting: “CONCLUSIONS: For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may [like: the sky MAY fall] reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.

    Also: “Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). RR = relative risk between statin and placebo pills.

    The Authorities may answer: ‘well the studies were underpowered’.
    Really? 20,000 women for years in randomized trials and no effect on
    mortality! How many more women does it take?

    To adamk Please go to the link above. What I am saying is that statins don’t extend women’s lives and that the numbers needlessly treated [NNyT] to prevent less serious events are truly massive and NICE gives no clue as to how massive. Since statins imitate nitroglycerin, they reduce angina chest pain. Since women don’t experience the typical male angina as much as men, that may just be the explanation why twice as many women needlessly are treated with statins than men to prevent non fatal events.

    Statins don’t deal with cause; they don’t add anti arrhythmic electrolytes [magnesium, potassium] or omega-3’s, and they don’t affect the strength of the artery that is determined by structural proteins.

    I don’t think most NICE panel members have anything but good in mind; they are misguided and bedazzled by the pharma herd that lives by the concept that cholesterol is evil. How do you expect a panel of these folk to counteract the spin of pharma [and Oxford U’s spin, financed by the >$m100 for statin research just from one Pharma]. Have YOU tried to
    understand the reasoning of NICE from the link above? Junk Science.
    Go to the trials and DO NOT use combined endpoints and see how well they work for women and then figure how well they may work for men. 3 new rosuva/Crestor trials: nobody saved from cardiovascular death. What can I say?

  39. retiredpharmaprof said,

    November 25, 2009 at 12:02 am

    erenard asked me to post this for him since his repeated attempts to post anything since yesterday have failed. Bizarre!

    To quasilobachevski: Janitors know that if something does not clean the floor, the stuff does not work. Anybody looking at female mortality in randomized trials knows that statins do not add minutes to a woman’s life in their top killing disease, cardiovascular disease. It does not take an Einstein to figure that out. Context does not matter: x dead women taking statin and y taking placebo, and with x = y when you add up all the studies.

    NICE’s context [method] is assigning ‘risk scores’ to and/or considering TIA [mini-strokes, lasting minutes with all effects, by definition, over <24 hours] as an equal value 'cardiovascular endpoint' to a non fatal [but often life altering if not debilitating] heart attack. Their
    context is inviting ALL statin manufacturers to comment and influence with one of their employees, Dr. Gibbs, on the NICE Appraisal Committee.

    That, my friend, is BadScience and a bad context.

    To Julie O.: women SHOULD be upset! Here’s a 2004 JAMA review about statins not saving their lives:
    www.ncbi.nlm.nih.gov/pubmed/15138247?dopt=Abstract
    Quoting: “CONCLUSIONS: For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may [like: the sky MAY fall] reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.

    Also: “Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). RR = relative risk between statin and placebo pills.

    The Authorities may answer: ‘well the studies were underpowered’.
    Really? 20,000 women for years in randomized trials and no effect on
    mortality! How many more women does it take?

    To adamk Please go to the link above. What I am saying is that statins don’t extend women’s lives and that the numbers needlessly treated [NNyT] to prevent less serious events are truly massive and NICE gives no clue as to how massive. Since statins imitate nitroglycerin, they reduce angina chest pain. Since women don’t experience the typical male angina as much as men, that may just be the explanation why twice as many women needlessly are treated with statins than men to prevent non fatal events.

    Statins don’t deal with cause; they don’t add anti arrhythmic electrolytes [magnesium, potassium] or omega-3’s, and they don’t affect the strength of the artery that is determined by structural proteins.

    I don’t think most NICE panel members have anything but good in mind; they are misguided and bedazzled by the pharma herd that lives by the concept that cholesterol is evil. How do you expect a panel of these folk to counteract the spin of pharma [and Oxford U’s spin, financed by the >$m100 for statin research just from one Pharma]. Have YOU tried to
    understand the reasoning of NICE from the link above? Junk Science.
    Go to the trials and DO NOT use combined endpoints and see how well they work for women and then figure how well they may work for men. 3 new rosuva/Crestor trials: nobody saved from cardiovascular death. What can I say?

  40. skyesteve said,

    November 25, 2009 at 9:34 am

    Wow! don’t know what’s gone on with this site – lots of duplicate entries. If that happens with this one then apologies in advance.
    @ Erenard – as said already I am sceptical about statins for primary prevention in general and certainly in women. I am also persuaded by the “They don’t reduce mortality in women in secondary prevention” argument too.
    However, the JAMA paper you refer to does say that in secondary prevention in women statins do reduce CHD events including non-fatal MI. Does that mean that they reduce morbidity? If so, is that to a sufficient extent to make prescribing them in women for secondary prevention worthwhile? I don’t know so would value your view.

  41. the rim groper said,

    November 25, 2009 at 9:55 am

    @quasilobachevski:

    Yes, your theory two is correct. I am obviously a fanatic. On the other hand, should you want to debate the science I am quite happy to do that.

    The issue is rather larger than a few hastily penned lines on a blog will address. NICE is just one tiny aspect of a much larger issue. The blog is entitled ‘Bad Science’ and the cholesterol/heart disease hypothesis IS bad science.

    The hypothesis was falsified from day one by its chief proponent. Ancel Keys claimed in his Seven Countries study that high cholesterol and heart disease were linked and his study was supposed to represent the vital evidence. The study excluded all of the countries which had populations that ate high fat diets and low rates of heart disease.

    The hypothesis does not even stand up to a superficial examination. If high fat diets cause high cholesterol, which in turn is supposed to cause heart disease, then how can the countries where a high fat diet is the norm, have low rates of heart disease?

    The director of the Framingham study, Dr William Kannel, stated publicly: “Framingham – Although there is no discernible relationship between reported diet
    intake and serum cholesterol levels in the Framingham Diet Study Group, it is incorrect to interpret this finding to mean that diet has no connection with blood cholesterol.”

    Two mutually exclusive clauses are used. Either there was a discernible relationship or there was not. I can assure you that if you were to eat 8 eggs a day for a month, the effect on your serum cholesterol level will be negligible, yet Framingham underpins the present day UK policy on the treatment of cholesterol. Please explain how that is good science.

    Statins inhibit the biosynthesis of cholesterol within the mevalonate metabolic pathway. Statins also inhibit the biosynthesis of Heme A which has nothing to do with cholesterol production. Statins inhibit the biosynthesis of Coenzyme Q10, which also has nothing to do with cholesterol production. Statins inhibit the biosynthesis of Dolichols, which have nothing to do with cholesterol production. statins inhibit the biosynthesis of prenylated proteins, which has nothing to do with cholesterol production.

    None of the other products mentioned has any role in the production of cholesterol and their roles are not subsidiary to cholesterol but just as vital. This game of treating cholesterol levels is wanting for the lack of logic. Hey, your cholesterol level is now great… sorry that the statins have induced programmed cell death, that your cells cannot derive energy from the food you eat, that cell communication is chaotic and that you cannot now make sufficient myelin to protect your neurological tissue.

    Most of the body’s cholesterol is found in the brain… perhaps because it serves no useful purpose. Your body controls your cholesterol level regardless of your diet. Why would it do that? Hasn’t your body heard that cholesterol is bad for you?

    Absolutely no-one has died, because they did not have enough statins sloshing about in their body. If you are seriously interested in learning more, you can scribble your e-mail address here… in a form that wont attract spam senders and net spiders and I will send you a very recent report.

    The report details that 100% of a number of statin users experienced adverse side effects to the point where 61% had to stop the drugs because of the severity of side effects. It also states that the number of patients who developed a serious neurodegenerative disorder was astonishingly high for the selected sample. 1:200,000 is the incidence rate of amyotrophic lateral sclerosis, for example. there were 18 cases in less than 400 people. Please explain that coincidence to me

    As to the situation with money being more important than healthcare, If you cannot see anything wrong with the manufacturers of drugs sponsoring drug efficacy studies and publishing the findings themselves, then I don’t much chance of forward movement. Do you recall Elsevier being caught red-handed? They had published several fake medical journals in an effort to stimulate the sales of pharmaceuticals.

    Where the drug companies are invited to help determine prescribing policies for their own products, then the opportunities for a corrupt manipulation are legion and the drug companies are not shy about taking them. They have more money to throw at marketing than would equate to the GDP of several countries.

    Merck’s own patent called for the addition of CoQ10 to their product and it was patented 20 years ago. Why is it not a routine practice? More appropriately, what was the damage that Merck wanted to ameliorate? Myopathy is the correct answer. You should read: United States Patent 4,933,165 Coenzyme Q10 with HMG-COA Reductase Inhibitors, June 12th 1990

    Remember that CoQ10 is one of the processes, which I mentioned earlier, that is inhibited by statins. It is certain that Merck knew that would be one effect of statins.

    Money and UK medicine? Look up the department of health stats for QOF payments, both for the cardiac domain and all domains and see how much extra cash a GP practice can make if it meets targets. Examine the drug company funded research projects in the UK.

    Yes. I am a fanatic and I make no apology for making every possible effort and taking every opportunity to prevent iatrogenic harm to patients.

  42. erenard said,

    November 25, 2009 at 11:41 am

    To skyesteve posting 40. Nobody would disagree that Lipitor in anybody and any statin in women do not change the date of death of the users.

    That leaves your question of morbidity, i.e. illness. Yes, statins reduce angina [proved Lipitor’s ASCOT study], as does nitroglycerin. Stable angina is ‘morbidity’ as is knee pain. Statins reduce the interventions that may well be driven by ‘innocent angina pain’. Don’t get me wrong: UNSTABLE angina [a unique pain sometimes increasing over days and not normally experienced] is dangerous and warrants an IMMEDIATE hospital visit but that is, in my appreciation of the data, NOT the kind prevented by a statin.

    The problem with NICE is that they don’t tell how many of a certain group and gender have to take statin to prevent one of what ‘event’. Moreover, there are at least 5 kinds of heart attacks, some silent, some not so much and the way studies are presented do not to help here. [ASCOT found no drop in ‘silent’, hospital detectable, heart attacks].

    So, to finally answer your question: no I don’t think in secondary prevention statins are worthwhile in women.

    They have untold and unknown side effects and distract from and ‘unmotivate’ people to deal with the REAL causes of arterial decline, heart attacks and heart failure. As says the American TV ad: “Now, I trust my heart to Lipitor”, removing the motivation to deal with harder to swallow changes. THAT is a never quantified side effect of statins but possibly one of the more serious ones.

  43. skyesteve said,

    November 25, 2009 at 12:11 pm

    I thought this forum was about evidence and, where possible, facts. So rather than rhetoric if you are really interested in the facts behind QOF payments for GPs here is QOF in all it’s glory

    www.nhsemployers.org/Aboutus/Publications/Documents/QOF_Guidance_2009_final.pdf

    Remember this is only part of the way in which GPs earn money and, with each QOF point earning £110, for most GPs this amounts to betweem 10 and 20% of total practice earnings (out of which they don’t just pay themselves but they also pay their reception staff, medical secretaries, practice nurses, managers, energy bills, maintenance costs, etc., etc.). I belive QOF has led to improved quality of care, at least here in Scotland.
    As you can see from the QOF document only one indicator in the CHD domain, CHD8, mentions a cholesterol target. None of the indicators mention statins at all. Again in the stroke domain a cholesterol target appears in one indicator, stroke 8, and their is no mention of statin anywhere. The only other domain where a cholesterol target is mentioned is in diabetes, DM17 but again statins are not mentioned anywhere. There is no mention of cholesterol targets in any of the other “cardiovascular” domains (primary prevention, hypertension, heart failure, atrial fibrillation and chronic kidney disease) and no mention of statins anywhere!
    GPs therefore do not get paid for prescribing statins. You could argue that they do get paid for chasing cholesterol targets but the amounts are trivial (perhaps about £200 per GP per annum) and, in many cases, we actually cho0se not to chase the target.
    I’ve read Gary Taubin’s book too and I do buy a lot of what he says. He’s right about selective evidence use. He’s right about the epidemic of sugar and refined carbohydrates in our diet. It’s been a year since I read it and it’s now with someone else but am I wrong in thinking that even he suggested a high LDL count was not a good thing? Is that true? And, if so, do statins help reduce LDL levels?

  44. erenard said,

    November 25, 2009 at 1:31 pm

    An anecdote: some years ago walking through some hospital corridor with one of the most known statin authors, I suggested: “what if most statin benefit would be derived from their nitroglycerin mimicking effect?” Without a pause he said .. “And we all know how many people THAT would save.” Well, he is one of the authors of the subsequent and probably THE most expensive statin study ever and that showed no benefit in cardiovascular mortality. I rest my case.

    For the science of this ‘nitroglycerin puffer’ NO effect, try this:
    Rikitake Y, Liao JK. Rho GTPases, statins, and nitric oxide. Circ Res. 2005 Dec 9;97(12):1232-5.
    www.ncbi.nlm.nih.gov/pmc/articles/PMC2633589/?tool=pubmed
    or
    Laufs U. Beyond lipid-lowering: effects of statins on endothelial nitric oxide. Eur J Clin Pharmacol. 2003 Mar;58(11):719-31. Medline 12634978

    I quote: Therefore, the ability of statins to improve endothelial function through the release of NO may partially account for their beneficial effects at reducing the incidence of cardiovascular events. These effects are real, unquantified and statins are not indicated to affect NO production; there are other, safer and more targeted pathways for that.

    This reality is something terrible to contemplate for those having hitched their reputations to the “cholesterol is evil and must be reduced at all cost” bandwagon.

    Strangely, the blog owner, psychiatrist Dr. Ben has remained quiet in this topic. Why not deal with NICE as a BadScience issue? If that is because he does not understand their “Bayesian statistics”, I don’t blame him: nobody does! Why not simply count the tombstones?

  45. the rim groper said,

    November 25, 2009 at 2:42 pm

    I have recently completed writing an informal report that may well have implications for medical practice in the UK. The information report gives an insight, inter alia, into the apparent incidence of major neurodegenerative diseases that may have been induced by HMG-CoA reductase inhibitors.

    Amyotrophic lateral sclerosis features in 18 reports among 351 people. The incidence is put at 1:200,000 according to the literature and this anomaly is not explained. A further 11 cases of progressive neurodegenerative conditions were also found in this small participant group which included Parkinson’s disease, Alzheimer’s Disease, Progressive Supra-nuclear Palsy and Chronic Inflammatory Demyelinating Polyneuropathy.

    Only clinicians will be able to decide on the value of this information and the implications for public health

    Download the report from this link: files.me.com/jeffcable1/x9fh5b

  46. adamk said,

    November 25, 2009 at 5:54 pm

    @erenard
    I read the link , and it certainly seemed to suggest that in women statins were of no proven help in primary prevention. It seemed to suggest that in secondary prevention it was beneficial for most of the outcomes , but not for over all mortality rate.
    However on the same page there was a link to another , seemingly well organised review suggesting that there were definite benefits with statins in both primary and secondary prevention (though not differentiating between men and women)
    There is a mass of data out there , and one could probably make a case for any viewpoint one chose to , by being selective with the data one looked at.
    Have there been any studies that set out to look specifically at the effect of statins in women? Isnt looking through the data after collection , and finding results , or lack of them in a particular subgroup (admittedly a large one) ‘bad science’. I expect if one looked hard enough one could always find a particular subgroup that was not affected in the same way as the whole population.

  47. the rim groper said,

    November 25, 2009 at 6:29 pm

    beep beep – Paging Dr Goldacre…

    You have raised questions and yet you have not returned to the debate you opened. IDo you have a problem with people not sharing your viewpoint?

  48. Ben Goldacre said,

    November 25, 2009 at 7:02 pm

    lovely long posts from the statin people.

    if i was going to write a long tedious article reviewing the academic literature on the effectiveness of statins, rather than a fleeting throwaway comment in a piece about the entirely different and interesting issue of failing to flag up side effects, i wld cheerfully have said that the evidence from subgroup analyses looking only at women is not as persuasive, moreso in results from older trials (iirc), possibly because the numbers of women in statins trials have generally been smaller, possibly because subgroup analyses can just throw up some weird results sometimes (as we’ve seen in previous columns), and possibly because women’s bodies respond to these drugs in a completely different way to men, which is possible, although that doesn’t seem hugely likely. but it’s certainly possible.

    relevant background here is that these are preventive drugs, preventing events that for each individual in each year are mercifully pretty rare, so the figures on deaths and heart attacks prevented will always feel thin, as i wrote about, eg in my piece on the way the benefits were overhyped in the JUPITER trial. everyone has to decide for themselves if they want to go through the bother of taking a pill every day that might make these fairly rare events a little rarer still, we’ll all have our own reasoning there, i don’t give readers health advice.

    i’d be grateful tho if the, er, lengthy frequent posters here could declare themselves properly. At least one of you has a very colourful website about the magical healing power of vitamin pills which i think everyone here would like to see. do post a link to it, please, and respect the rules of the site, which are pretty friendly and reasonable. cheers.

  49. julie oakley said,

    November 25, 2009 at 11:48 pm

    Thank you for responding Ben. Being an artist of very little brain, I really need to see someone’s blog/website or whatever before I can tell what I really think of their ability to pronounce on scientific matters, so I’d almost definitely like to see the which one of you has the lovely vitamin pill web site.

  50. the rim groper said,

    November 26, 2009 at 12:53 am

    BG: lovely long posts from the statin people.

    TRG: do you have any point to make?

    BG: i’d be grateful tho if the, er, lengthy frequent posters here could declare themselves properly.

    TRG: Had you followed my previous link: files.me.com/jeffcable1/x9fh5b

    you would have seen that I have declared myself. Which site rules have I transgressed?

  51. adamk said,

    November 26, 2009 at 11:59 am

    @the rim groper

    “The report details that 100% of a number of statin users experienced adverse side effects to the point where 61% had to stop the drugs because of the severity of side effects.”

    Its not very surprising that 100% of people who have reported side effects have experienced side effects.
    Your report seems like alot of anecdotal evidence from a self selecting group. It doesn’t really consitute strong evidence. Sorry.

  52. the rim groper said,

    November 26, 2009 at 12:51 pm

    @adamk

    Perhaps you have misunderstood. Every single patient on a statin had experienced side effects. Now we are told that side effects are rare and that serious side effects are very rare. I cite the incidence of amyotrophic lateral sclerosis as 1:200,000 according to the Neurology research paper and in 351 cases there were 18 incidents.

    I explained and acknowledged the limitations of an informal report and you seem to have missed that five paragraphs which appeared immediately after the background information.

    Notwithstanding that, your comment is unworthy of a clinician, if that is your work: I don’t suppose that 18 people gave themselves ALS in order to become part of a self-selected group for the purpose of completing a survey telling the world how they have developed a progressive and fatal condition.

    As for your apology, it is as irrelevant as you so obviously are. These are ordinary people reporting what has happened to them. The report is designed to inform you, not to massage your huge ego and permit you to feel superior to anyone who is not you.

    I sincerely hope you that never develop ALS or any other iatrogenic debilitating and progressive disease for that matter and hopefully, you wont hear someone else pass a similar judgement on the rationale with which you would want to inform others.

    [deep sigh]

  53. Arrowheed said,

    November 26, 2009 at 1:11 pm

    TRG: GGGGGGRRRRRRRRRRRRRRRRRRR AAAAAAAAAAAAAAHHHHHHHHHHHHHH.

    AH: Settle down and stop referring to yourself in the 3rd person.

    TRG: AAAAAAAAAARRRRRRRRRRRRRGGGGGGGGGGGGGGGGHHHHHHHHHHHH GGGGGGGGRRRRRRRRR

    AH: Pop yourself a statin before you have a heart attack.

  54. adamk said,

    November 26, 2009 at 2:27 pm

    @ rim groper
    Obviously I’ve upset you , I’m sorry for that , and I didnt mean to belittle your report which must have taken an enormous amount of time and effort. That however doesn’t make it strong evidence.

    i’ve had an inkling for a while that you may have experienced personally some of the statin side effects that you mention? The fact that they are rare isn’t any consolation to the people who get them. However being personally affected doesn’t make one the best candidate for appraising their worth.

  55. Veronica said,

    November 26, 2009 at 3:17 pm

    “So a drug company has been able to delay the inclusion of safety warnings on a drug prescribed to 4 million people, for 21 months, because they didn’t agree with the wording. There is no conceivable world in which this is a good thing.”

    What if the drug company was RIGHT??? I work for a drug company and I know the kind of thing that the MHRA and its sister agencies around the world want us to put on “product labels”. e.g. a certain disease causes some patients dizziness. Some patients with that disease who are taking your product report dizziness in a clinical trial. There’s no evidence that the drug causes the dizziness, the patients would have got it anyway, even if they were on placebo. But the agencies want you to write “MAY CAUSE DIZZINESS – CAUTION: DO NOT DRIVE OR OPERATE MACHINERY… etc.” on your patient information leaflet.

    The trouble is, the drug industry is not generally allowed to talk to patients about the benefits of their products. Patients are too stupid to understand, so companies can only talk to doctors about the good stuff. However in the patient leaflet we have to breeze over the potentially life-saving “benefits” section in a trice and then list out a whole range of low level, rare side effects in enormous detail. Knowing the human mind’s capacity for making risk:benefit judgements, that makes all drugs seem so evil that patients who are prescribed them frankly are frightened to take them. That is why a pharma company might have objected to the decision of the agencies.

  56. erenard said,

    November 26, 2009 at 3:19 pm

    Dear Ben: by a method that escapes me you figured out my identity and suggest I have a colourful website [thank you] about the “magical healing power of vitamin pills”. First: it deals with micro-nutrients, including vitamins, and its subtitle is ’cause and prevention”, not “healing” heart disease, although there is evidence for that. This >10 year old not-for-profit site sells nothing but provides free info.

    Looking at our motives and backgrounds, we clearly have more in common that what divides us. I missed your analysis of JUPITER so if you have a link, please.

    Since the elegant and open minded Julie O would like to see my take on ‘vitamins’ I feel obliged to. Here it is, the summary page: www.health-heart.org/simple.htm
    For Ben, the science: www.health-heart.org/why.htm and
    for anyone’s critique, my take on statins et al:
    www.health-heart.org/cholesterol.htm with here JUPITER / rosuva
    www.health-heart.org/JUPITER_Table_3_Outcomes.gif
    For some hard vitamin benefit: www.health-heart.org/HIPandHOPE.gif
    For those curious about my person and record:
    www.health-heart.org/author.htm ; Email vos{AT}health-heart.org

    This DISTRACTION from the subject at hand was NOT my choice which is why I used a variation of my name.

    The name of the website is “Nutrition, Health & Heart Disease; Cause & Prevention”. It is after having looked the matter of ’cause’ for decades that I was forced into dealing with the fallacy of cholesterol.

    I’d agree with our host that the ‘supplement business’ is no more ethical than Pharma and they are joined at the hip. ‘Vitamins’ are basically controlled by Bayer, Roche and some other Pharmas, and the Chinese. Micro-nutrients, however, can and do affect ’cause’. Moreover, probably less than 1 American/year dies from the IMproper use of ‘vitamins’ versus 1 each and every 5 minutes in a hospital setting from the PROPER use of drugs [reported JAMA]. Pick your cure, or windmill.

    Let’s debate ‘vitamins’ when NOT talking statins. Ben: your next BadScience target has to be that NICE document!

  57. the rim groper said,

    November 26, 2009 at 3:51 pm

    @Arrowhead

    AH: Settle down and stop referring to yourself in the 3rd person.

    TRG: Four occurrences of the first person singular.

    AH: Pop yourself a statin before you have a heart attack.

    TRG: Dear me, what an unpleasant character you are.

  58. the rim groper said,

    November 26, 2009 at 4:18 pm

    @adamk

    Thanks for the apology. I must have seemed a bit prickly and I apologise for being hypersensitive. Of course, the whole point of the report was that it was not the hard data of a fully controlled, double blind research study. The anecdotal accounts were just self-reported experiences. The fundamental question remains: should those anecdotal accounts be ignored because they were not the numbers collected by Pfizer or Merck inspired and funded research? I happen to think that clinicians should not ignore those accounts. They were remarkably congruent and consistent with each other.

    What it leaves is a summary of the personal accounts (the soft-edged numbers) and an uncomfortable feeling that adverse reactions are more common than supposed hitherto. The incidence of ALS, for example, is not on all fours with what is known about ALS. The MND association in the UK puts the incidence of ALS/MND at 2 cases per 100,000so 18 cases still looks too high, to my mind. How can we explain the anomaly?

    The total of neurological adverse reactions was confirmation that inhibition of Dolichols, Heme A, Coenzyme Q10 and prenylated proteins is not a good thing. The science does not support the notion that cholesterol is the principle actor in cardiovascular disease, and it never did,save in the minds of Ancel Keys and Dr William Kannel.

    I would like to commend the work of Professor Bruce Ames and his co-workers to you. His work is illuminating in the field of Mitochondrial oxidative decay and apoptosis. his understanding of Heme A depletion is second to none and it underpins the inability of the cells to derive energy from the food we eat. Low cholesterol predicts higher mortality than high cholesterol.

    I have never taken a statin (too long a story for this blog) and I have not yet developed CHD. Of course I avoid visiting my family medical practitioner because he wont like my 8.8 total cholesterol or my mild hypertension nor will he like my high fat, low carbohydrate diet. It has helped me to lose weight without even trying. In turn, I wont be medicated needlessly or because of government targets. Blanket Rx for whole populations is not the practice of medicine but it is most assuredly the practice of the expedient and one would hope that the medical profession is much better than that.

  59. bodenca said,

    December 4, 2009 at 8:46 pm

    Have things quietened down?
    You know how it is when you’re settling to accepting somebody’s line, and then, right at the end, they blow it?

    If I collect bivariate data and you find out I ditched half before correlating, you have no usable information. (Not strictly true when you know which corner of the plot I ditched, but let’s not quibble.) However, if I ditch identifiable cohorts of data, the logic is quite different.

    The rim groper tells us the Seven Countries Study disregarded states with low heart disease and high fat diets. As I see it, this still leaves:
    1. In the Seven Countries, there is a positive correlation between high fat and heart disease.
    2. High fat/cholesterol is not the principal cause of heart disease.
    3. Whatever the real principal cause is, it afflicts the populations of the Seven Countries.
    4. When the principal cause is present, high fat/cholesterol exacerbates its effects.

    He now admits to high blood cholesterol and an intentionally high fat diet. I deduce that
    Either he knows the true principal cause of heart disease, and why he’s safe from it, but he isn’t letting on,
    Or he doesn’t appreciate the points above and is inadvertently risking his health,
    Or he is deliberately perverse.

    Quite separately, I have trouble reconciling his statement that statins are completely ineffective (as supported by Erenard) with Skyesteve’s “the number of heart attacks and strokes in our practice has plummeted … since we started using statins on a widespread basis”.

    So, while I could accept The rim groper’s arguments about “side” effects and wrong reporting of statins, I’m wary of accepting his whole story.

  60. reprehensible said,

    December 12, 2009 at 12:21 pm

    Yeah thats pritty bad but the NHS still probably takes the record. PROMS (Patient reported outcome measures) data has only begun to be collected in NHS hospitals from April 2009. This has not been done since the time of Florence Nightingale and the Lunacy act of 1845. BUPA started in 1999 but they didn’t wanna pay for bad workmanship :-P

  61. bogmailer said,

    December 29, 2011 at 10:11 pm

    Bodenca,

    Maybe you should read The Cholestrol Myth or Fat & Cholestrol Are Good For You both by Uffe Ravnskov MD PhD & have a look at www.thinsc.org

    In particular this item:

    people.csail.mit.edu/seneff/why_statins_dont_really_work.html