Unbiased review concludes that statins do not have overall benefits for healthy people

It’s often said that the ‘gold standard’ test of a medical intervention is the ‘randomised controlled trial’. If it was a drug being tested, this normally means randomly assigning half of a group of people to the drug, while the other half gets a placebo. In ‘double-blind’ studies neither the researchers nor the study subjects supposedly know who is taking what until the ‘code is cracked’ at the end of the study. These studies look like a pretty watertight and very dependable way of assessing treatments, but they are not necessarily as reliable as we might imagine.

To begin with, it’s sometimes possible for researchers to ‘work out’ who is likely to be taking what, which can jeopardise the results of a study. For example, let’s say the drug being tested is a statin (cholesterol-lowering drug). Researchers may have access to the study subjects’ cholesterol levels and assume that those whose cholesterol levels fall significantly are taking the statin while those whose levels stay the same are not.

The real issue here is that this may then affect, even unconsciously, decisions the researchers make which ultimately may affect study results. For example, researchers may recommend that patients on the placebo are at greater risk and might be more inclined to recommend that they undergo more aggressive treatments such as angioplasty (expansion of a coronary artery with a balloon) or insertion of a stent (termed ‘revascularisation’ procedures’).

Another problem is that these revascularisation procedures also increase the risk of complications including heart attack. The end result of all this is that those on placebo may end up ending worse outcomes and the drug now looks better than it is in reality.

Another example of bias concerns study length. Usually, how long a study will be continued for is decided in advance. Sometimes though, the ‘code is cracked’ before the end, and if the results favour the active treatment it can be deemed unethical to continue and allow not to have access to a treatment that might benefit them (the active drug). However, it is well known that early termination of trials tend to exaggerate the benefits of a treatment, and downplay the potential harms.

Overall, such biases favour the drug being tested, so sometimes researchers attempt to take this into account when assessing studies.

I recently came across a relevant review of statin therapy published in Therapeutics Letter produced by researchers at the University of British Columbia [1]. The researchers were specifically looking at the effect of statins in ‘primary prevention’ (in individuals without a prior history of cardiovascular issues such as heart attack or stroke). Previous reviews had found mixed results, it seems at least in part because some of these reviews included studies which themselves included individuals who did have a previous history of cardiovascular problems. The benefits of statins are generally greater in those with pre-existing disease and their inclusion in primary prevention studies biases the results in favour of statins.

The authors of the Therapeutics Letter review took out such studies, and also removed studies that seemed most subject to other forms of bias. Their final analysis revealed that while statin therapy, overall, led to a 21 per cent reduced risk of serious heart disease-related problems (e.g. fatal or non-fatal heart attack), overall risk of death was not reduced at all. Neither, it turns out, was risk of total ‘serious adverse events’ (this includes not just heart attacks, but ‘side-effects’ such as muscle damage or liver damage).

The authors point out that if the heart benefits of statins do not translate into a reduction in total serious adverse events, then statins must be increasing the risk of other (adverse) events to an extent which completely negates their positive heart effects. This fact is reflected in the last line of their conclusions which reads:

Statins do not have a proven net health benefit in primary prevention populations and thus when used in that setting do not represent good use of scarce health care resources.


1. Do statins have a role in primary prevention? An update. Therapeutics Letter March-April 2010. Therapeutics Initiative University of British Columbia

11 Responses to Unbiased review concludes that statins do not have overall benefits for healthy people

  1. Barry Danser 19 October 2012 at 10:09 pm #

    I have stopped my statins I feel better and the weakness I was feeling in my muscles seems to be a lot better . The trouble is the same doctor who told me 5years ago they were compulsory then told me the argument I made to him at that time has a point! Well done him for admitting he may have made an error but how long have we got to be guinea pigs

  2. Diane Smith 19 October 2012 at 11:09 pm #

    Can you look into this please Dr Briffa?

  3. Eddie Mitchell 19 October 2012 at 11:24 pm #

    Hi John

    So, “Unbiased review concludes that statins do not have overall benefits for healthy people” Statins don’t do much for unhealthy people either. Most recently, two separate studies have concluded that progression of coronary artery calcification, which is the hallmark of potentially lethal heart disease, is INCREASED with statin drug use. A new study in the journal Atherosclerosis shows that statin use is associated with a 52 percent increased prevalence and extent of calcified coronary plaque compared to non-users.

    These disturbing findings come right on the heels of another study published in the journal Diabetes Care, which discovered that type 2 diabetics with advanced atherosclerosis who are frequent statin users have significantly higher amounts of coronary artery calcification compared to less frequent users of the drug.

    The authors concluded that: “More frequent statin use is associated with accelerated coronary artery calcification in T2DM patients with advanced atherosclerosis”


    Keep up the great work.


  4. Doc´s Opinon 20 October 2012 at 1:25 am #

    I agree that we do have to be careful when prescribing statins in primary prevention because the science is not conclusive: http://www.docsopinion.com/2012/06/19/should-i-take-cholesterol-lowering-drug-2/.

    However, I believe the data is very conclusive when it comes to secondary prevention, such as post MI, although Dr. Briffa certainly highlights some of the problems with clinical trials. It would be irresponsible to ignore the data on statin use in secondary prevention. That would be going against evidence based medicine.

    I have seen the studies that Eddie is referring to concerning statins and coronary calcification. They do raise some questions and concerns, not least because they contradict results from previous studies. Although the magnitude of coronary artery calcification is an independent risk factor, we have to remember that atherosclerosis involves a number of other mechanisms. Coronary calcification may indeed be more related to stable than unstable coronary artery disease, the latter involving mechanisms such as plaque rupture and thrombosis. The studies referred to are not reason enough to stop prescribing satins in secondary prevention.

    Furthermore, It is possible that there are different mechanisms behind coronary calcification and coronary artery narrowing. In one metaanalysis, coronary calcification was not affected by statin therapy although there was a consistent moderation of progression of coronary artery narrowing with statins. http://www.ncbi.nlm.nih.gov/pubmed/20843566

  5. moyper 20 October 2012 at 11:50 pm #

    In response to Barry D. “Error” seldom comes in to it. GP prescribing practices are based on financial gain. You are extremely fortunate (far more than you know) that you were not hit with the ‘keep taking the pills’ injunction. The force-feeding of statins is a medical crime against humanity.

  6. Chris 21 October 2012 at 3:26 pm #

    The studies referred to are not reason enough to stop prescribing satins in secondary prevention.

    I take your point, Axel, that trials and results testing the effect of statins in primary prevention do not necessarily equate to ‘evidence’ that is applicable to the decision tree of secondary prevention. I imagine by ‘primary prevention’ you refer to ambition to prevent CHD in people who haven’t suffered a CHD event, and ‘secondary prevention’ applies to people have suffered a prior CHD event. À mon avis, statins are prescribed upon spurious pretenses in both primary and secondary settings. Here’s how I come to that that opinion.

    The theory goes that high levels of cholesterol in the blood will be spirited into a layer just beneath the arterial wall and will accumulate as atherosclerosis, or ‘fatty plaques’. The process by which this could happen has yet to be properly and reliably described, and as the majority of the bodies cells can synthesise cholesterol for themselves the pathway doesn’t have to be exclusive to that of liver, cholesterol, or LDL-lipoprotein.

    The theory or hypothesis that associates saturated fat, cholesterol, and incidence of CHD was founded in a big-fat mistake (see next paragraph) later compounded by a leap so great it was big-fat speculation. Then when Ancel Keys was challenged to support his hugely speculative hypothesis he returned with a big-fat lie that in which he cheery picked seven data points from 22 to result in the graphical presentation of association that supported his otherwise unsupported hypothesis.

    Millions of dollars have been ploughed into CHD research. Despite gargantuan efforts no study has returned an unequivocal result showing a clear association to support the hypothesis; and why would they when the foundations for the hypothesis involved a confounding factor that the effects of oxidised cholesterol in the chow fed to some lab-bunnies were mistaken for the effects of cholesterol itself? And why would they if the key proponent himself had no supporting evidence, but returned with some that was plain fraudulent? In order to expedite ambition Keys lost sight of rightful scientific curiosity, and almost all interest in cholesterol since has fallen for the same malaise. Science that should commute to the science of understanding has been commuted to the science of manipulation.

    The test that supposedly reports cholesterol counts isn’t a test for cholesterol at all. The ‘lipid profile test reports’ counts of lipoproteins and divides the counts into factions. Since lipoproteins are the principle method involving the carriage of crucial lipids and proteins around the bodies super-highway defined by the vascular system they deserve respect. They’re so darned ingenious and such amazing natural grace. What brings a molecule of glycerol to bind with three lipid molecules to form a triglyceride? .. .. .. Tnd what brings these triglycerides to agglomerate in the core of a lipoprotein in the company of cholesterol to be sheathed by an outer body formed by the conjoining of apolipoproteins and phospholipids? Under what influence do these molecules assemble to form an ingenious macromolecule that overcomes some challenging logistical challenges? Could cholesterol be a kind of nucleic seed? Does something about cholesterol offer an unseen attraction to the lipophilic aspects of phospholipids so that the hyrdophilic aspects of phospholipids are arranged to face outermost and can thus disperse in the blood?

    Furthermore if not following the pathway to being used as fuel the least reactive fats are distributed along with cholesterol to form the basis and structural integrity of all cell membranes. In accord, subtle variations to the structure of membranes modulates the degree of permeability that determines what may pass into the cell to be metabolised or support internal cell function or what must be kept out. Then the more reactive fats are distributed to be assimilated into eicosanoids that are fundamental signaling molecules of the autocrine system, and the basis around which some immune system responses, including modulation of membrane permeability, are constructed. All these processes and functions must involve pathways in which lipoprotein interactions must be early steps.

    The lipid profile test may well be instructive where it is a feature of trials. But the instruction pertains to many potential features of a lipoprotein and not singularly to cholesterol. The outrageous aspect in this is that possible lessons that may pertain to lipoproteins are ascribed to cholesterol. Mention of LDL-cholesterol in any context is an affront to the rigour and regard required by science and scientific method.

    Studies have struggled to prove association, and intervention trials have struggled to result in intended outcomes for the simple reason neither saturated fat nor cholesterol have any significant causal involvement in the advance of CHD. The fact that summaries frequently misreport what the study has actually establsihed, and that statistical shenanigans are used to overstate supposed benefits, is disgraceful. There was one study that did result in significant positive outcomes and that was the Lyon Diet-Heart Study led by Dr. Michel de Lorgeril.

    This dietary intervention study did successfully reduce mortality from heart disease but ‘proved’ cholesterol had no part in this because ‘cholesterol’ was identical in the groups at the start and at the end of the trial. I am somewhat reticent to report this because, as is commonplace, the metrics involved measuring lipoprotein counts which, as you should be aware, constitute a proxy method for the metering and recording of cholesterol counts.

    The Lyon Study indicated quantitative arrangements involving cholesterol have no discernible bearing. Possibly quantitative arrangements involving lipoproteins have little or no bearing. But some quantitative and qualitative variations in diet might. At the end of the study the intake of omega-6 PUFAs was twenty times higher than intake of omega-3 in the control group. In the intervention group with striking positive results the omega-6 oils exceeded omega-3 by only four to five times. The study was stopped early because early results showed such striking disadvantage to the control group it was considered unethical to continue.

    It was in the 1970s that animal experiments tested effects of cholesterol and oxidised cholesterol demonstrated that dietary cholesterol is innocuous whereas oxy-cholesterols are highly deleterious. This led Kilmer McCully to direct that the early Russian experiments on rabbits need to be reinterpreted. Since these results fascinated Ancel Keys and led him up the garden path, so does the whole cholesterol hypothesis. The decision to prescribe stains with the intention of reducing cholesterol synthesis is far from evidence based.

    The indications are that stress and oxidative stress sit causally behind CHD and other conditions. CHD has the look of resulting from a chronic, but otherwise natural, immune response to insult or injury where the insult or injury may come from alternate directions but commute to otherwise quite similar physiological responses involving oxidative stress, inflammation and down-regulation of immune function. Small wonder ill-founded interventions directed at CHD result in a rise in all cause morbidity or mortality including and not limited to cancer. Statins interfere with the synthesis of other vital biochemicals.

    How much reason do you need Axel?

    By way of disclaimer I’m in no way medically qualified; instead I work in logistics and transport, and I understand the relevance of size of vehicles to issues in distribution. If parcels are to come to my door, invariably they arrive in a small vehicle, and invariably they were once conveyed in great big one, like the one I drive. The sizes of lipoproteins, often equated to ‘densities’, are almost certainly associated with function and ‘intended delivery addresses’. That makes for systemic sense. Unfortunately, and under certain conditions, lipoproteins may be involved in the carriage of lipids that have been subjected to stress and oxidation.

    Einstein lent a definition of insanity: repeating the same thing over while expecting a different result each time. It reveals his disdain for peoples whose regard for cause and effect is selective and not universal. Turn that around and we can lend a definition for folly.

    Folly: Intervention in the dominion of things that are improperly understood. Expecting a desired outcome and being willfully blind when the desired outcome does not result. Or delivering the desired result while excluding the likely possibility that undesired outcomes, noticed and/or unnoticed, may arise in tandem.

    The war on cholesterol is misguided and folly. Within the campaign exist vicarious liabilities so great that few associating with the folly dare concede the absence of mandate. Feel free to develop and self-trial a suppository variation on the statin theme, but be clear they do not appeal to me taken orally or otherwise, neither do plant sterols.

    This advocacy is delivered in good faith without prejudice, Axel, my only aspiration is that it will be assistive. And I hope Dr Briffa would concur it is not at odds with the directions arising from the study he discusses.

  7. Stacie 22 October 2012 at 8:55 pm #

    The death knell for statins continues to ring. I say that there is no benefit in secondary prevention. Every trial since 2005 has been a failure. Absolute risk reduction for mortality is less than 2% in trials conducted before 2005. These were trials paid for, conducted by, controlled by, etc. the pharmaceutical industry. This feeble benefit is questionable as well as clinically insignificant. Much better results can be gotten by using fish oil and other supplements. The statin drug run will eventually end; the writing is on the wall.

  8. Barry Danser 25 October 2012 at 9:14 am #

    Moyper lets not get too ahead of ourselves here.
    I agree there is a danger that GPs as a collective unit may well force statins onto clients for monetary gain.
    However in the last 5 years my doctor (the same doctor who stood outside my house waiting for me to arrive back from France after a heart attack 10 years ago) did three things

    1. Changed his mind about Statins being the problem solver
    2. Revised his thoughts in favour of low carb diets
    3. Told me to join Dr Briffa!

    So if there is a plot to put us on statins (and i don’t doubt it) not every GP will lie down and accept it.

  9. Janet 28 October 2012 at 11:36 pm #

    @Doc’s Opinion:
    “It would be irresponsible to ignore the data on statin use in secondary prevention. That would be going against evidence based medicine.”
    Ben Goldacre’s recent book has highlighted what has been known for years to independent researchers about “evidence-based” medicine – that it is often anything but.
    “The studies referred to are not reason enough to stop prescribing statins in secondary prevention.”
    Maybe not, but if we accept that the rather small reduction in absolute risk when statins are used in secondary prevention is due to anti-inflammatory effects rather than reducing blood cholesterol levels per se, how much more useful might it be if doctors suggested real, valuable, life-enhancing ways to reduce inflammation in the arterial wall such as ensuring that dietary intakes of antioxidants and essential fats are optimised, and consumption of sugars reduced?

  10. mamaprophet 31 October 2012 at 7:26 pm #

    My sister has been on statins for years, she has had many many problems with her health (heart disease, high blood pressure etc) she suffers terribly with with muscular pains and now her statins have been increased. She has recently been sent as an emergency patient from her surgery to the hospital because they feared she may be having a heart attack, so what good are these statins doing her????

  11. Dave Wyman 10 February 2013 at 10:42 pm #

    Chris wrote:

    “Einstein lent a definition of insanity: repeating the same thing over while expecting a different result each time.”

    Except Einstein never said that.

    Excellent post, Chris, however your reliance on believing what you want to believe – e.g. the Einstein quote – makes the rest of what you say somewhat suspect. It makes me wonder if you aren’t cherry picking some of the evidence of your own assertions.

Leave a Reply