Magic bullet or massive missfire?

Forty years ago Henry Gadsden, chief executive of the drug company Merck, expressed his frustration that the potential market for his company’s products should be limited to those with treatable illness. Ideally, he said, he would like ‘to sell to everyone’. ‘Henry Gadsden’s dream has long since come true,’ observes the medical commentator Ray Moynihan. ‘The marketing strategy of drug companies now targets the hundreds of millions of the apparently well, persuading them they have some medical condition that warrants treatment.’

The jewel in the crown of modern pharmaceuticals and the apotheosis of Henry Gadsden’s vision of selling ‘to everyone’ are cholesterol-lowering statins. They are the wonder drugs of our age, credited with saving tens of thousands of lives and generating for their manufacturers £15 billion a year in annual revenues. They are, by far, the single most profitable drug ever discovered. Already the most widely prescribed class of drugs in Britain, they could soon become even more so following the recent recommendation by a committee of cholesterol experts advising the National Institute for Health and Clinical Excellence (Nice) that those eligible for statins should be extended to everyone aged 60 and over, boosting the numbers taking them to an eye-watering 12 million — or one in four of the adult population.

Intuitively, this seems a bad idea for any number of commonsensical reasons but, claims Sir Rory Collins, Professor of Medicine and Epidemiology at the University of Oxford, ‘The evidence supports these recommendations — the drugs are effective.’ He concedes that some ‘may not like the idea of mass medication’ but they can be reassured at least that statins have been found to have ‘virtually no side effects’. Dr Judith Finegold of the National Heart and Lung Institute, in a recent, much-publicised study scrutinising nearly 80,000 patients, found the incidence of symptoms commonly attributed to statins to be no different from those of volunteers taking a placebo.

Both Sir Rory Collins’s endorsement of the benefits of statins and Dr Finegold’s reassurances about the low incidence of side effects are based on the findings of drug company-sponsored clinical trials — not perhaps the most reliable source of evidence, given their well-known reputation for consistently reporting ‘favourable efficacy and safety results’.

Professor John Abramson of Harvard Medical School has a rather different take, drawing attention in a critical review in the British Medical Journal last year to the main difficulties in assessing the findings of these clinical trials. First, the claim that statins are ‘effective’ conceals the minuscule benefit they confer on the vast majority for whom they have ‘no significant effect on overall mortality’ (in other words, they do nothing to prolong life in the majority of people taking them). Statins reduce the absolute risk of heart attack and stroke in just 2 per cent of cases. The outcome in those at ‘high risk’ (with markedly elevated cholesterol levels or a previous history of circulatory disorders) is only marginally better — preventing a further episode in just 4 per cent, with a 1 per cent reduction in ‘overall mortality’.

Thus the promotion of ‘statins all round’ — given these modest benefits — could really be justified only if indeed they have ‘virtually no side effects’. This is hotly disputed. Statins were in the press earlier this month after the British Medical Journal accepted that it had published flawed research last autumn over-estimating the side effects of statins. The research had claimed that 18 to 20 per cent of patients suffered debilitating side effects, and this statistic has now been withdrawn by the authors. But while their figure may have been an over-estimate, that doesn’t necessarily mean statins have no side effects.

Indeed, this would be most unlikely — not least, as Professor Abramson observes, because it appears that some clinical trials may have excluded patients unable to tolerate the drugs. It is certainly contradicted by independent surveys of those taking statins that suggest the prevalence of muscular aches and pains to be 100 times greater than reported in trials, along with numerous other problems of fatigue, depression, poor memory and concentration, sleep disturbances and reduced libido.

I first became aware of the scale of this hidden epidemic of apparent statin-induced symptoms after describing in my Telegraph column the experience of a man in his seventies whose general health following the successful repair of an aortic aneurysm had gradually deteriorated to a state (as he described it) of ‘chronic decrepitude’ — such that when flying to Hawaii to attend his son’s wedding he had required a wheelchair at the various stopovers. Yet returning three weeks later he had walked back through Heathrow — having forgotten to pack the statins he had been taking since his operation.

This account of his near-miraculous recovery following his statin-free excursion prompted hundreds of letters and emails from readers describing their own similar experiences. Those who had been previously fit and well were usually quick to spot the adverse effects on their wellbeing: ‘Within a couple of weeks I went from an active 65-year-old to a doddering old man,’ as one put it. Most only realised the devastating impact of statins on their lives when advised by friends and relatives to stop taking them.

Thus the ‘bottom line’, as Professor Abramson describes it, is that for more than 95 per cent of those taking statins, they neither prolong their lives nor prevent serious illness while some may experience side effects ranging from the ‘minor and reversible to the serious and irreversible’.

Abramson’s trenchant critique of this unprecedented experiment in mass medication — and its consequences — raises the question of how it has come about. Here two distinct, if interrelated, factors are highly relevant. The first is the progressive entanglement and blurring of the boundaries of interest between the pharmaceutical industry and the medical profession. Many of the ‘key opinion leaders’ (or KOLs as they are known to the industry), the senior physicians and experts involved in one way or another with evaluating and promoting the widespread use of statins, have ties with the drug companies that manufacture them and are rewarded for their efforts. Next, if more obscurely, the argument for widening the constituency of those taking statins is predicated on an influential, if speculative, theory much favoured by epidemiologists and public health experts known as ‘the population approach’. This maintains that, rather than focusing efforts on those at ‘high risk’, the prevention of common illnesses – such as heart disease – is best achieved by lowering the average cholesterol level in everyone (‘the population’).

Within this context it is possible to trace the rise of statins over the past 30 years, starting with the presumed link established back in the 1980s of the causative role of cholesterol in circulatory disorders — the thesis that those indulging in (for example) bacon and eggs for breakfast raised the levels of cholesterol in the blood and this in turn clogs up the arteries, increasing the risk of a heart attack. The imagery is powerful, if simplistic. There is (perhaps surprisingly) no correlation in the pattern of heart disease over the past 60 years with trends in the consumption of ‘high fat’ foods such as meat and dairy products. Cholesterol cannot be entirely innocent, even if it plays a vital role in many bodily functions. Those with a genetic defect resulting in markedly elevated levels are undoubtedly at greater risk of heart disease.

The many attempts to encourage people to switch to a ‘healthy’ low fat diet were not successful, prompting a switch of emphasis in favour of cholesterol-lowering drugs. The results of the trial of the first statin, Lovastatin — developed by Henry Gadsden’s company and launched in 1987 — were certainly encouraging in this regard. Soon enough several other drug companies, recognising its bounteous potential, came up with their own versions and in the subsequent scramble to secure a share of this lucrative market, the clinical trials assessing their efficacy were transformed into an ingenious and highly successful form of marketing. Organised on a massive scale involving up to 10,000 patients, their favourable results — announced with great razzmatazz at major medical conferences — generated an almost evangelical zeal for the project of ‘statins for all’.

Meanwhile, successive expert committees charged with establishing ‘clinical practice guidelines’ have invoked the principle of ‘the lower the cholesterol the better’ to reduce the cut-off point for initiating treatment to well below the ‘normal’ or mean cholesterol level — expanding by millions the number eligible for statin therapy. Doctors were still free to use their clinical judgement as to whether or not to adhere to these guidelines. But this changed in 2003 when the Department of Health, strongly influenced by the proponents of the ‘population approach’, linked general practitioners’ remuneration to their success in achieving predetermined targets obliging them to assess the ‘cardiovascular risk’ in all their patients and prescribe medication to lower it. Circulatory disorders are strongly age-determined, so general practitioners can maximise their income by the simple expedient of routinely prescribing statins to the elderly — who are, of course, more vulnerable to their potential side effects.

By now it will be apparent that in one way or another a considerable proportion of the medical profession from the KOLs to humble general practitioners, epidemiologists and public health doctors are committed to supporting statins — and they have no avenue of retreat. They can scarcely concede it might not, after all, be a good idea to prescribe potent drugs to vast sections of the population. And it has recently emerged that statins, besides everything else, may also cause diabetes in almost 2 per cent of those taking them — a small percentage, one might think, until one does the sums and realises this adds up to more than 5,000 new cases a year, and 27,000 over a five-year period. And diabetes, as we all know, is a serious condition, not least in predisposing people to those circulatory disorders the statins are intended to prevent — along with impaired vision, neuropathy and impotence.

The drug companies have obviously played a central role in orchestrating the rise of statins. That is only to be expected and indeed one can almost imagine the shrewd Henry Gadsden admiring the elegance of the strategy with which his successors have realised his vision — recruiting those KOLs to the cause and exploiting to their considerable advantage the epidemiologists’ ‘population approach’ and government policy on the remuneration of family doctors. Many might rightly be concerned at the unflattering insight into the current intellectual state of medicine where doctors should so uncritically endorse the findings of industry-funded clinical trials.

But there is more than this. Biology is complex and the biology of cholesterol very complex, since cholesterol is the foundation for several important hormones and integral to the structure of cell membranes. There is little doubt that it plays a role as a contributory — if not determinant — factor to circulatory disorders, but it is folly to suppose it might be possible to reduce its concentration in the body without running into unexpected problems.

I am haunted by an image drawn from the many experiences of readers related to me over the last few years. It is of a woman in her mid-seventies whose physical aches and pains, progressive immobility and deteriorating memory are, her family doctor has advised her, only to be expected at her age. That evening before retiring to bed she takes a daily dose of the most commonly prescribed drug in Britain.

  • Puss in Plimsolls

    Surely the paragraph involving bacon and eggs was the place to comment that refined carbohydrates, eaten to excess, cause disease. (See Gary Taubes.) The obsession with “fiber”/fibre (always bizarre to me) was also accompanied by a ‘population’ approach — doing a lot of harm and very little good. Everything was blamed except starches and, to a lesser extent, the more obvious evil of excess sugar, even though the idea that lots of sweet cakes make you fat was one that went back into the 19th century….

  • Glyn Wainwright

    As cholesterol is beneficial and vital, what exactly is it that statins claim to do, apart from create a wide-range of problem caused by cholesterol depletion in all major organs and tissues?

  • david

    I was trekking in Nepal at age 69. Before breakfast, up 1500 feet to see the sunrise, down for breakfast…and then the day’s 8-hour trek, continuously up and down steep crumbling stone stairways. Six short months on 20 mg of simvastatin, and I can’t even stand at a counter for 15 minutes without severe pain–both then and for days thereafter. My legs muscles look like deflated balloons. I have shocking (to me too) photographs, if anyone care to see. I’m in constant pain: muscles, joints, and nerve pain. My case is said to be rare. How would anyone know? My doctor refuses to acknowledge any relationship to the drug. And yet the onset on my symptoms (tightening of Achilles, foot cramps, calf cramps, numbness in feet, etc) are exactly what so many others describe. Now, of course, I’m “getting older”. Odd that my upper body is still strong, while my legs are progressively rotting beneath me. Horrifying! For someone else’s profit–like asbestos, tobacco, cocaine. david

  • Picquet

    Thanks for worrying me. Having had a heart attack 17 years ago, I’ve been prescribed the things ever since, and although I’ve complained about weird effects (that could really have been caused by other things, such as alcohol, or interactions with other little pills) and been switched to three or four other types of stain, at varying strengths, I’m unwilling to stop taking them completely!
    It does seem that our KOLs are split on their true effects; perhaps a new miracle drug is in the making which will align their opinions. Meanwhile, I’ll keep pounding the treadmill. And guzzling the wine; life’s too short anyway.

  • sasboy

    I am a medical doctor and I can tell you statins work wonders in reducing cholesterol, both for Primary Prevention – preventing heart attacks and strokes – as well as secondary prevention – reducing the likelihood of repeat heart attacks and strokes in people who have already have had them.

    Please stop misguiding people. Statins are a godsend and have helped millions of people worldwide.

    • Sign your name then, doc.

    • MJHopeC

      Sasboy (Dr)

      Some facts.

      Collins HPS study went to great trouble to EXCLUDE all statin intolerants, potential intolerants, non-compliants etc. to ensure that the incidence of adverse reactions was low. Indeed, the process was highly successful, BUT HIS ATTEMPT TO EXTRAPOLATE THIS RESULT TO THE GENERAL POPULATION IS GROSS BAD SCIENCE.

      In fact, the whole study and its use to support the general medication of the population is grossly flawed. As I have pointed out to NICE, the HPS study with its highly selected test sample (merely ~30% of the initial sample) is only valid with respect to patients that would meet the exclusion/inclusion criteria of the study. Thus, the promotion of the study for the general population is grossly flawed, if not deliberately fraudulent.

      Let us also look at the title which included the phrases “Heart protection” and “cholesterol lowering”. The report does absolutely nothing to support this contention. The data must include the cholesterol levels in various sub-groups of both treatment groups. The ones I am most interested in are the “no-event patients”, the “non-fatal event patients” and the “dead patients”. These groups are identifiable. If the cholesterol hypothesis is correct, then the cholesterol levels for each sub group should be:

      [no-event patients]<[non-fatal event patients]300. This, not surprisingly, is the same as that found in Collins HPS trial; a NNT per annum > 300 (estimate 156 saved / 10269 /5 years per annum). Why was this basic result confused by introducing 3 million?

      Another feature of misdirection and result hiding lies in the fact that 781 died despite treatment in the stain group. This is a massive 83% of the expected death rate based on the placebo death rate (781/937*100) leaving a paltry 17% efficacy rate. Why was this not reported as a basic result of study? More obfuscation perhaps? Where is the “TRUE” results claimed by Collins?

      Finally, there is no mention of the fact that statins are pleiotropic
      The Sever study ( is similarly flawed. There was no significant difference in all cause mortality (Table 2 All-cause mortality Atorvastatin dead=185 (3.6%) Placebo dead= 212 (4.1%); p = 0.1649 NS not significant); ie., no life extension – 0.5% difference

      Much more interesting is the cardiovascular death rate from Table 2. (Cardiovascular mortality Atorvastatin dead= 74 (1.4%); Placebo dead=82 (1.6%); p = 0.5066 – NS) 0.2% difference. No benefit for cardiovascular death rate.

      AND THIS STUDY WAS TERMINATED EARLY! I wonder why – real reason please

      AND YOU STILL BELIEVE THAT STATINS ARE WONDER DRUGS – critical thinking seems to have deserted some of the medical profession.

      • sasboy

        Thank you for this feedback. I will provide you a link to just one study conducted by the British Medical Journal which shows that statin use is associated with reduced cardiovascular mortality in primary care and in the primary prevention of cardiovascular pathology –

        • MJHopeC

          A meta-analysis??  Unfortunately the primary assumption of statistics is random selection.  The criteria for SELECTING studies breaches that assumption.  The data I sent you are from RCTs using random selection; admittelly in  the HPS study the final group was selected (thus restricting its value to those patients who would meet the exclusion/inclusion criteria.  The results are clear enough and are repeated in many studies.
          Statins have a trivial benefit and a substantial risk of  adverse reactions up to and including Alzheimer’s but if AD was acknowledged it would bankrupt Big Pharma.  Hence studies that show a statin association with  AD are rigorously rejected as I know to my cost.

          • UKSteve

            Oh dear, a “meta-analysis”? Like the one they used to “prove that carbon dioxide is warming up the Earth causing climate change”? That nonsense?

            My previous general practitioners were nothing but drug pushers – their answer for everything was ‘go an a drug, then keep increasing the dose until your on the maximum, if that stops working, we have others’.

            For years they tried to get me to start on statins, despite telling me that my “good and bad cholesterol levels were good, but me good to bad ratio was really good” ! So why the ***k do I need statins?

          • MJHopeC

            Hi Steve

            Epidemiological studies are extremely useful for identifying possible associations (even sometimes causes).  However, they have to be coherent and consistent as stated by Prof. Bradford-Hill many decades ago;  a feature so often missing in the current rash of studies.
            This subject is admirably dealt with in Dr. James LeFanu’s book under the title of “Social Theory”.  The book is well wort reading!

          • UKSteve

            Yes I’ve been familiar with James Le Fanu’s writings for a good few years. Many thanks for the recommendation 🙂 ; I will get hold of a copy.

    • UKSteve

      Why was my previous GP surgery pushing them onto me, when every blood test showed me that my bad cholesterol was ‘good’, by good cholesterol ‘quite good’, and my ratio of bad to good was ‘very good’? I am 48.

      • sasboy

        I would not be able to answer that question unless I have your numbers in front of me.

        • UKSteve

          A lame response – why would anyone with “very good” cholesterol control need statins? You’re no more a doctor than I am, probably just a shill or hireling for Big Pharma.

          The only evidence you offered was a BMJ article – the house magazine of the BMA. ‘Nuff said.

          MJHopeC has completely rubbished your posts.

          • sasboy

            Try an American article instead –


            FYI, practice in the US and put my patients on statins all the time and I have the guidelines of the NCEP ( National Cholesterol Education Program ) to support my attempts to bring their numbers at goal.

          • UKSteve

            I can’t read it – it requires a login. And I stand by my original charge.


            (By the way, a vascular surgeon specialises in surgery on blood vessels.)

            Oh, and six of the nine panelists on the government Cholesterol Education panel have received grants or consulting or speakers’ fees from companies that

            produce statin drugs. These companies stand to profit considerably from the panel’s recommendations. When the consumer watchdog organization Public Citizen’s Health Research Group blew the whistle on this conflict of

            interest, the coordinator of the panel called the omission of financial disclosures an “oversight.”

            So…. are you in sales for Big Pharma?

          • sasboy

            Are you a medical professional ? The way you speak suggests not.

          • UKSteve

            Nope. Just a very interested party.

            But I “sound far more like a medical professional” than you do – you haven’t a clue it seems, and still haven’t answered my question.

          • sasboy

            I put my patients on statins all the time with excellent results and they are tolerated well. Get a life and get over your statin obsession.

          • UKSteve

            My mother’s cat is more of a doctor than you are. You’re a spamming, troll-fraud who probably didn’t even graduate high school.

            Think you ‘re a doctor? Go and see one; you need to, but it’s not statins you need.

          • sasboy

            Rather obvious from the way you talk your mother’s beloved cat serves both as a role model and a source of information for you.

          • UKSteve

            And rather obvious from your imbecility that you don’t realise you’ve just made an utter cnut of yourself on the internet.

            And yes, the cat is still a better “doctor” than you are. “Doctor” …..pfffff! Go and see a psychiatrist.

          • sasboy

            Do you consider the hundreds of thousands of doctors prescribing statins and other life saving drugs to be “imbeciles” too ?

            I would have suggested you to see a Psychiatrist as well, except you probably don’t trust them either. You can stick to your mother’s cat for all I care…..

          • UKSteve

            Well, as I keep repeating, ‘tardo, it’s more of a doctor than you are.


    • Cholesterol is GOOD for people (unless it’s VLDL, of course). The fear of it that most people have is unwarranted, even dangerous. Most people now view cholesterol as if it were cancer, and that’s the lie told by the doctors they trust.

  • moyrart
  • MJHopeC

    Comment Re: The US NHBLI (Dr Finegold) is hand in glove with Big Pharma. Some years ago they and the US CDC announced that there was an epidemic of congestive heart failure and the figure they produced clearly mimicked the rise in the use of cholesterol lowering drugs. This web page rapidly disappeared but was found again on the “thinkquest” site but has since been archived. I am assured by an American cardiologist that the epidemic is still extant.

    Can someone tell me why this wep page was removed – seems to me to be more evidence of Big Pharma pulling strings.

  • sasboy
  • al_mas

    I am 63 and my fasting bs is 5.6 which I keep under control via diet. Recently I was prescribed first Crestor, then Lipitor. Within 2 months my cardiologist says I am diabetic having had twice a fasting bs of 7 and he recommended metformin. I read up and am convinced it was Crestor and LIpitor but he did not want to listen. I then did my own research and switch without his knowledge to pravastatin. My fasting bs is now 5.4 to 5.6, my usual but the statin is giving severe muscular pain and I am slowly working towards getting off it altogether.
    My point is I pity all those who are in their 60s and 70s who suddenly develop T2 diabetes unknowingly as a result of long term statin use and have their quality of life severely affected and this side effect was neither communicated or monitored. If I had not done my research I would be diabetic today.