The ‘Cochrane Collaboration’ is an international collective of researchers whose self-proclaimed role is to provide accurate and robust assessments of health interventions. The group specialises in ‘meta-analyses’: the grouping together of several similar studies on interventions including drug therapies.
In 2011, Cochrane researchers assessed the evidence relating to statin use in individuals at low risk of cardiovascular disease (defined as a less than 20 per cent risk over 10 years), and concluded that there was limited evidence of overall benefit [1]. I appeared on Channel 4 news to discuss this publication and the issues surrounding it, and you can see the discussion here.
Earlier this year, the same Cochrane group updated their data and concluded thatoverall risk of death and cardiovascular events (e.g. heart attack or stroke) were reduced by statins in low risk individuals, without increasing the risk of adverse events (including muscle, liver and kidney damage) [2]. It seems the Cochrane reviewers had had quite some change of heart. A paper published in the BMJ on 22 October questions the evidence on which this U-turn appears to have been made [3].
The authors of the BMJ piece note that although the 2013 meta-analysis included four additional trials, these trials did not substantially change the findings. The change in advice was actually based on another meta-analysis, published in 2012, conducted by a group known as the Cholesterol Treatment Trialists’ (CTT) collaboration [4].
Among other things, the CTT authors concluded that, in low risk individuals, for each 1.0 mmol/l (39 mg/dl) reduction in LDL-cholesterol, statins reduce overall risk of death and heart attack by about 9 per cent and 20 per cent respectively. The conclusion was that statins have significant benefits in low risk individuals that greatly exceeded known risks of treatment.
However, the CTT authors took the odd step of calculating the benefits of statins according to a theoretical reduction in LDL-cholesterol levels. A much more realistic appraisal would be simply to calculate if, compared to placebo, statins actually reduce the risk of health outcomes.
The BMJ authors use the data from the CTT meta-analysis and found thatrisk of death was not reduced by statins at all. So, the CTT authors had used had extrapolated the data in a way that showed a benefit that actually does not exist in reality.
And what of the claim that statins reduce the risk of cardiovascular events such as heart attack or stroke? The data shows that about 150 low-risk individuals would need to be treated for five years to prevent one such event (i.e. only about one in 750 individuals will benefit per year).
They also draw our attention to the impact of statin treatment on ‘serious adverse events’. This outcome can be improved by statins as a result of, say, a reduced number of heart attacks, but worsened through side effects such as muscle or liver damage. The BMJ authors note that the CTT review did not consider serious adverse events (a major omission). Without knowing more about this, though, we simply cannot make a judgement regarding the overall effect of statins, and whether the net effect is beneficial or not. Interestingly, of three major trials that were included in the CTT review that assessed overall serious adverse effects, none found overall benefits from statin treatment.
So, while the CTT authors seem to have over-hyped the benefits of statins, they seem at the same time to have been quite keen to steer clear of talk of their very real risks and the absence of evidence foroverall benefit.
The BMJ authors draw our attention to the fact that every single trial included in the CTT was industry funded. Such trials are well known to report results more favourably and perhaps downplay risks than independently funded research. The BMJ authors cite specific ways in which the adverse effects of drugs seen in clinical trials can be ‘minimised’. These include:
- The exclusion of individuals from trials with known health issues likely to be exacerbated by statins or signal susceptibility to statin side effects (such as liver, kidney and muscle disease).
- The use of a ‘run-in’ period before the study starts which detects and then excludes individuals who do not tolerate statins.
- The possibility that individuals ‘drop out’ from the study because of side effects, meaning that the incidence of some side effects can be ‘lost’ from the data.
- Failure of the study investigators to assess and monitor adverse events such as muscle damage and changes in brain function.
- Failure to properly ascertain or report adverse events.
It is noted that the Cochrane authors admit the reporting of adverse effects in studies is generally poor, but also state that it’s unlikely statins have major life-threatening hazards. The authors of the BMJ piece are not convinced, though, writing: “[The] large discrepancies between the frequency of adverse events reported in commercially funded randomised controlled trials included in the CTT meta-analysesand non-commercially funded studies show that determination of harms cannot be left to industry alone.”
The BMJ piece is accompanied by an editorial from the journal’s editor, Fiona Godlee [5]. Her comment on this issue starts:
None of this does much to bolster confidence in the published literature.
Godlee goes on to write:
Nor am I reassured by discussions at two recent meetings co-hosted by the European Federation of Pharmaceutical Industry Associations (EFPIA). Drug company AbbVie is suing the European Medicines Agency to stop summary reports of its clinical trials becoming publicly available. AbbVie’s lawyer made clear that the company considers even the data on adverse events to be commercially confidential. Despite industry’s claims to be in favour of greater transparency, EFPIA and its American counterpart PhRMA are supporting Abbvie. The BMJ and BMA have joined forces to intervene on behalf of the EMA.
If I were to summarise, I’d say that, at best, there seems to be a degree of complacency regarding the veracity of statin data on the part of both the CTT and the Cochrane researchers. There is a sense that they are happy to present the ‘positive’ findings in the best possible light, and at the same time seem relaxed about the clear gaps we have in our knowledge about potential harms. The fact that statins appear to have no overall benefit in those at low risk of cardiovascular disease should not go unacknowledged, either.
Worse still, we have evidence that drug trials can be designed, conducted and reported in ways that obscure the truth. And sometimes, even when we have data that can help us make informed decisions about the appropriateness of a treatment, some drug companies will fight tooth and nail to prevent that data seeing the light of day.
This sort of subterfuge may be good for sales and share price, but it is almost certainly bad for our collective health. On this point, the BMJ authors state than instead of doctors following guidelines and prescribing statins for individuals at low risk of cardiovascular disease, they should explain the magnitude of benefits and uncertainties regarding harm. In addition, they might also discuss the fact that the vast majority of cardiovascular disease risk is linked with lifestyle factors such as smoking, diet and physical activity. Fiona Godlee backs this approach, but states that the benefits of lifestyle change are: “something that the dominance of industry sponsored clinical trials too often obscures.”
Personally, I am delighted that the misdeeds of drug companies and some researchers can now be exposed in this way, and in a high-profile medical journal at that. In the past, I think there was much more opportunity for the industry and its hired hands to mislead us. Greater transparency means that the industry as a whole is getting more of what I believe it deserves: our contempt.
References:
1. Taylor F, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2011;1:CD004816.
Medline
2. Taylor F, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev2013;1:CD004816.
3. Abramson JD, et al. Should people at low risk of cardiovascular disease take a statin?
BMJ 2013;347:f6123
4. Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. The Lancet 2012;380(9841):581–90.
5. Godlee F. Statins for all over 50? No BMJ 2013;347:f6412.
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I wonder how many articles, blog posts, books, proper trials and other media stories it will take before the misuse and over prescription of statins is finally halted?
My husband doesn’t know what to do now, he stopped his statins again, his GP was aghast and told him he NEEDED to take them, he restarted and had a headache 4 days in a row. He stopped them and his headache went. He reads your articles, he is convinced (I think) that he doesn’t need them but he just can’t quite get past his GP being so certain he should take them. He’s an intelligent, well read man, what hope is there for those who still have GPs on a pedestal and think everything they tell them is gospel?
I see Sweden has become the first country to change it’s advice about saturated fats and will promote them as being beneficial. I’m not sure the Finns will follow suit, they make Benecol lol.
I read that polyunsaturates were given to transplant patients as they function as immune suppressors, but that the practice was stopped after the patients developed cancers.
Ref: Chapter 5 Trick and Cheat, Barry Groves.
About 3 years ago i was prescribed statins but they produced painful feelings in my thigh muscles that prevented me walking any distance. I stopped them and the condition went away.
My health history is of high blood pressure, treated by a cocktail of drugs. I have had a heart stoppage (2009) on an operating table whilst undergoing a Hernia repair. No explanation for that was forthcoming, but I suspect the anaesthetist made a mistake. A little later I apparently had a TIA (tingling in my right arm) I was admitted to hospital for tests which confirmed the event.
My present GP now wants me to go onto a different statin (Avorvastatin).
I have deep misgivings about Statins, but my doctor insists that they may be life saving.
I really do not know what to do!
Is there any guidance that you can give me?
Mal Ranson
Any suggestion that cochrane has fallen prey to the same industry carrots?
Shalom,
The BASIC problem with medicine & medical research today is, DOCTORS WORSHIP MAMMON.
They are IMMORAL when it comes to RESEARCH & PRESCRIBING OF DRUGS.
The Drug Companies have been fined 4 to 5 BILLION dollars repeatedly for underhanded research, but they pay the fine & continue “pushing” their crap medicine.
They are multimillionaire Snake Oil Merchants!
NOTHING HAS CHANGED FROM THE DAYS THEY OPERATED FROM THE BACK OF A LORRY!
The patients are getting sicker & the hospitals are always full.
If medicine had advanced, we would see the opposite!
Today doctors take the HYPOCRITICAL OATH, rather than the HIPPOCRATIC OATH.
God, protect us from doctors!
Any comments anyone- regarding the role of statins in delpetion of fat-soluble antioxidants, and uptake of Co-enzyme Q10 (ubiquinol); how this is used in subcellular enzyme activities particularly within the mitochondria of muscle cells? Thank you in advance.
How the results of drug trials that are so orchestrated can then be used to advise doctors to prescribe statins (or any other drug, for that matter) for the public in general is despicable. Furthermore, I personally know of several friends and relatives who, when asked if they have had any memory issues since starting statins, have indeed found lapses in memory, confusion, some having problems finding the right word – which they put down to ‘age’ – but working backwards have now realised the problems started with the statins. Unfortunately this particular side effect is played down, even though it has now been added to the FDA data sheet. The problem is that the real numbers of people affected may never be known as firstly the patient hasn’t been alerted to it and therefore doesn’t associate the problem with commencement of statins and secondly, if they do notice a correlation and mention it to their doctor, the latter dismisses it as something that wasn’t likely to have been caused by the drug, and certainly won’t suggest the patient stop the statin and see if their memory problems etc improve. So the post-marketing side effects of this nature don’t get reported back to the MHRA or the drug companies.
However, simultaneously the numbers of people with ‘dementia-type’ symptoms is increasing, not just because we are living longer because many people who are still middle-aged are beginning to notice these kinds of symptoms……could they be on statins?
And, again, I ask…how do you find a doctor (in the United States) that “gets it!” I am having absolutely no luck and my current “doctor” is holding me hostage unless I take his prescribed statin. I wish I could play the voicemail I got from him when I told him I could no longer afford to take Livalo. I said, since I didn’t believe in the value of the drug anyway, at least he could do was prescribe me one that was “affordable.” His message said (quite lengthy) that he was going to prescribe me a generic statin, but that is would NOT protect me from stroke or heart attack and that my complaints of muscle pain would more than likely increase. Pffft. I guess Kowa Pharmaceuticals pays him more than I do.
Don’t worry it will all be forgotten about when the PCSK9 inhibitors come out their final trials and another round of even lower cholesterol lowering will begin.
Board rooms are buzzing with excitement at who will win the latest block buster marvel drug.
Denise, you might do well to read Dr. Stephen Sinatra’s books. He’s apparently a well known and eminent cardiologist in the States who has gone into great depth about cholesterol and heart disease. I have read his book Reverse Heart Disease Now. It was hugely interesting and takes the information down to cellular level. He doesn’t completely condemn statins but he is not a routine scriber either. In fact he believes that statins are useful, just not necessarily for heart issues or cholesterol.
My next read will be his book on cholesterol, The Great Cholesterol Myth – Why Lowering Your Cholesterol Won’t Prevent Heart Disease-and the Statin-Free Plan That Will. Maybe I can find something positive in there that will persuade my husband that he should ditch his statins for good and maybe give him something with which to argue back at his GP.
Another good blog to read is DrJackKruse.com. You may not want to buy into his thinking but on his forum there is a lot of info about what tests you can order to find out a lot more about your health. I think you’re lucky in the States, there’s not much like that available in the UK and what there is, is hugely expensive.
Thanks Sue G for mentioning Dr Stephen Sinartra’s book, ‘The Great Cholesterol Myth’. I have bought it and it is beginning to open eyes! Many thanks…
“None of this does much to bolster confidence in the published literature.”
Well said. But where does it leave us?
Hi
Can anyone provide links to any research or just advice around statins and type 1 diabetes?
I’m 36 YO type 1 diabetic (25 years) and my Dr is now applying serious pressure to take statins but I refuse. Partly as I already know of the lying by omission and general deceit/fraud of Big Pharma and too many anecdotal stories of side affects of Statins.
I’m very fit, I strength /condition train 4 x week, I’m 13% body fat, my diet is clean, I avoid wheat/sugar/processed foods, my Hba1c for the last year has been 39 (with infrequent hypos amounts), My LDL was 5.9, my post prandial blood sugar is excellent, generally lower than 7.8mmol an hour after eating.
I have no family history of heart disease, heart attacks, strokes. I aim for 8000+ steps a day (I don’t drive), I’m low carb throughout the day and only eat higher carb post workout. I cook every single meal I eat from fresh. My diet is essentially (mainly organic) vegetables, meat (organic/grass fed/ free range when possible), mackerel, wild salmon, herrings, olive oil, coconut oil, grass fed butter, 85% chocolate, full fat milk kefir, quality cheese, occasional nuts and seeds and a cup of coffee a day.
I have zero diabetic complications (other than Candida but I recently managed to stop Candida symptoms by using coconut oil topically and eating a teaspoon raw a day. Miraculous!)
Basically I’m pretty much as good a specimen of a patient as a diabetic type 1 of 23 years can be. I see my doctor 15 mins once every six months. He doesn’t believe cholesterol is the cause of heart attacks, nor do I, and he’s insistent I take Statins. He ‘doesn’t know how they work, but they work’.
Advice. Help. Ammo. Links for research. Needed. I’m a lay person and I need ammo to shoot down his zealot like approach to wonder that is statins.
Either that or I just sit in his office and say nothing for 15 minutes, which would be awkward. Thanks in advance.
Greg I’d like to live in your house please 🙂 try as I might, I can’t persuade my husband to eat as well as he might and he is type ll. If you head back to some of Dr. Briffa’s early blogs on statins he links to a lot of research, see he end of most of his blogs.
You might look at the aforementioned book by Dr. Sinatra or visit http://www.jackkruse.com for a vast number of blogs that can be very technical but are also very informative. Dr. Gary Taubes is also good for a view and links.
Have fun and up your coconut oil, it’s amazing stuff, not for nothing is it called The Tree of Life 🙂
Further to the BMJ article…
http://www.huffingtonpost.com/david-h-newman-md/statins_b_4277001.html
and
http://www.nytimes.com/2013/11/14/opinion/dont-give-more-patients-statins.html?_r=0