The Science of Statins: Well, This Is Awkward.

I’ve been ignoring the “statin controversy” for a while now, because 1) the accepted guidelines are actually pretty damned clear and well-established, and 2) the kind of people and websites that are excitedly discussing it seriously also seem to be the kind that set up all sorts of false dichotomies between The Goodness of Nature and The Evils of Drugs.

But I’ve noticed a few doctors who are taking this all very seriously – one cardiologist at our hospital is taking all of his female patients off statins – so… what the hell.  I went ahead and looked into it.  And now I feel reasonably confident I can give you a Cliff’s Notes version of what everyone’s fighting about.

Spoiler alert: … holy crap, I think the dissenters have a valid point.

Main Arguments of The Current Statin Controversy:

1.  There’s no proof that statins actually lower all-cause mortality.  Many of the most famous studies use very soft end-points (like “need for revascularization”) in addition to hard end-points like “myocardial infarctions” or “death due to adverse cardiovascular events” or just “death”.  In many cases (I’m looking at you, JUPITER Trial), the end-points wouldn’t be statistically significant if it weren’t for the inclusion of the soft end-points.

If you think about it, all-cause mortality is really the end-point that should matter – especially in light of the growing evidence that statins hugely increase your risk of diabetes (especially for women) and are correlated with an increased incidence of cancer.

2.  The absolute risk reduction may be statistically significant, but it’s TINY.  I have a lot of reservations about this point.  Their argument is that drug companies are only reporting the relative risk-reduction (which means that if, for example, the rate of heart attack went from 2% to 1% on a statin, the relative risk reduction would be 50% while the absolute risk reduction would be 1%), which is false and deliberately misleading advertising.

But then these same people (ahem, Dr. Barbara Roberts) will rather hypocritically go on to use absolute numbers when discussing the adverse effects (i.e. “Statins increase the risk of myositis 50%!” instead of “Statins increase the risk of myositis from 1% to 2%), which frankly makes me want to hit them across the head with a large biostatistics book.

Personally, I think a 1% absolute risk reduction in absolute mortality isn’t “paltry” or “only barely statistically significant” if it’s YOUR absolute mortality that we’re talking about – but that’s just me.

Still, there does seem to be an arguable point that many of the biggest studies (for example, the JUPITER trial – which, interestingly, was regarded as a huge success for statins overall), showed no decrease in absolute mortality at all.

3.  The adverse effects of statins are horrific.  True – but a lot of this is based on very specific stories about very specific patients who had bad experiences (Dr. Barbara Roberts is especially guilty of this – it’s actually kind of embarrassing to the medical profession, in my opinion, to put that much emphasis on “Well, I heard this one story about a lady who NEARLY DIED” as opposed to the actual percentage likelihood of that happening, but whatever).  It’s still worth knowing that there’s a statistically significant increase in risk of developing diabetes if you’re on a statin [3], though – especially in light of point #4, which is:

4.  There is ZERO evidence that statins reduce strokes or MIs in women.  This was shocking to me.  It’s true.  There’s a statistically significant effect when men and women are lumped together, but if you look at women’s end-points separately from men’s, you’ll find there’s no statistical merit whatsoever.

An exception that is often raised is the JUPITER trial, which was initially heralded as showing a statistically significant decrease in end-points for women.  The problem is, there was no reduction in risk of fatal OR nonfatal heart attacks, or fatal or nonfatal strokes.

… which is sort of the point, isn’t it?  Instead, it’s only because the study authors included “need for revasculization” in their studied endpoints that any statistically significant advantage was found to rosuvastatin at all.  There was no difference in mortality or adverse CV events.  (Also: no women below the age of 60 were included in this trial.  So, there’s that.)

(This isn’t true for secondary prevention, though.  If a hyperlipidemic woman has already had a thrombotic stroke or MI and is looking to prevent another one, that’s a different story – though it’s true that the risk reduction is still less than it would be for men.)

4.  You can accomplish the same thing with diet and exercise.  Yes, but easier said than done.  Unless you’re an incredibly gifted motivational guru of a doctor, it’s kind of a drastic oversimplification.

5.  Drug companies are paying for all these studies – they’re inherently biased.  Personally, I doubt this makes the studies more biased than any other kind of research – no matter where the funding comes from, everyone’s careers are staked on a positive result.  But okay; valid.

6.  The Cholesterol Hypothesis is faulty.  Most medical professionals shy away from this one, but it’s out there, and it’s… not entirely wrong.  We do have surprisingly little evidence that cholesterol levels directly correlate with risks of adverse cardiac events – but that’s exactly the sort of study that would be really difficult to pull-off.  Correlation vs. causation is never easy.

The bottom line is that there’s ZERO evidence for putting women on statins for primary prevention – no matter how many risk factors they have.

And that’s… kind of mind-blowing.

Sources:  1. K.K. Ray et al, “Statins and All-Cause Mortality in High Risk Primary Prevention: A Meta-Analysis of 11 Randomized Control Trials Involving 65,229 Participants,” Archives of Internal Medicine, 170, no. 12 (June 28, 2010): 1024-31

2. J. Downs, et al., “Primary Prevention of Acute Coronary Events with Lovastatin in Men and Women with Average Cholesterol Levels: Results of AFCAPS/TexCAPS,” Journal of the AMA 279, no. 20 (May 27, 1998): 1615-22.

3. S. Mora, et al., “Statins for the Primary Prevention of Cardiovascular Events in Women with Elevated High-Sensitivity C-Reactive Protein or Dyslipidemia: Results from the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and Meta-Analysis of Women from Primary Prevention Trials,” Circulation 121, no. 9 (March 9, 2010): 1069-77.

4. M. de Logeril, et al., “Cholesteral Lowering, Cardiovascular Diseases, and the Rosuvastatin JUPITER Controversy: A Critical Reappraisal,” Archives of Internal Medicine 170, no. 12 (June 28, 2010): 1032-36.

5. “Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels: The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group,” New England Journal of Medicine 339, no. 19 (November 5, 1998): 1349-57.

6. “MRC/BHF Heart Protection Study of Cholesterol Lowering with Simvastatin in 20,536 High-Risk Individuals: A Randomized Placebo-Controlled Trial,” Lancet 360, no. 9326 (July 6, 2002): 7-22.

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17 thoughts on “The Science of Statins: Well, This Is Awkward.

  1. Great stuff. Thanks for putting the research together, something all of us, myself included, should do more often. What I’ve come to find is that in many cases the rationalist faction of doctors aren’t any more scientific or critical in their thinking; they mostly just rally around the fashionable causes. Many of these causes are correct, but quite a few are questionable at best.

    Just because the opposite faction includes many idiots (antivaxers and the like) doesn’t mean that the “evidence-based” crowd has put any more thought into it. I hope you continue to do this kind of first-principles research and share the results!

  2. #5 is actually very important. remember vioxx. big pharma controls the studies and statistics of their studies purely for their own profit.

    • I’m not sure you realize that the data from all of these studies is publicly available. So a non-pharma person really can go and do their own analysis on it if they wanted to. Sadly, it’s easier for people to throw out conspiracy theories and ad hominem attacks, so the hard work often never gets done.

      • Ad Hominem commentary is normally considered false logic. If this attribute applies to this particular argument it flies in the face of some powerful proponents. Here are two only, and there are hundreds more if you take the time to research. Review the Pharma studies all you like; the data is manipulated and unreliable.

        *************************************************************
        **http://www.ccjm.org/content/78/6/393.full (Cleveland Clinic Med Journal)

        A SHORT EXCERPT FOLLOWS:

        Why is statin-induced myopathy so uncommon in clinical trials?
        A reason may be that patients in clinical trials are carefully screened. To minimize toxicity, the clinical trials of statins excluded patients with renal insufficiency, hepatic insufficiency, a history of muscular complaints, and poorly controlled diabetes, as well as patients taking drugs with possible interactions. Large efficacy trials have excluded up to 30% of the participants in active prerandomization phases.13,14

        ************************************************************

        **http://abcnews.go.com/Health/HeartHealth/cholesterol-busting-statins-study-raises-concerns/story?id=11037926#.T9NyAbBfF68 (ABC News Report)

        A SHORT EXCERPT FOLLOWS:

        Nearly two years ago, a study known as the JUPITER trial hinted at a new era in the use of statins — one in which the cholesterol-busting drugs could be used to stave off heart-related death in many more people than just those with high cholesterol.
        Now, however, researchers behind a new review that takes a second look at the findings of the landmark study say that these results are flawed — and that they do not support the benefits initially reported.

        *************************************************

        And here’s one from Cornell Law School:

        http://scholarship.law.cornell.edu/cgi/viewcontent.cgi?article=1318&context=facpub&sei-redir=1&referer=http%3A%2F%2Fwww.google.com%2Furl%3Fsa%3Dt%26rct%3Dj%26q%3Dstatin%2520study%2520false%2520reporting%26source%3Dweb%26cd%3D6%26sqi%3D2%26ved%3D0CF4QFjAF%26url%3Dhttp%253A%252F%252Fscholarship.law.cornell.edu%252Fcgi%252Fviewcontent.cgi%253Farticle%253D1318%2526context%253Dfacpub%26ei%3DPXXTT8_SDMna2wX_o-ylDw%26usg%3DAFQjCNET1_kyF56_991bilnWSLeZ8_b90g#search=%22statin%20study%20false%20reporting%22

        *****************************************************

        It IS true, as stated in your remarks, you can get informed if you take the time to review the research findings. Make certain though you consider both sides of the argument.

        Brooks

            • I understood your comment to state I could look at the data provided by Big Pharma research and arrive at a reasonable conclusion. As the data is skewed, any conslusion based on that data would be unreliable. If I misunderstood, I apologize. I have a short fuse where Pharma studies are involved. Please consider myremarks “friendly fire”.

              Brooks

              • with you Brooks, the data are skewed and unreliable. i resent the one person calling all dissenters to say
                vaccines as “idiots”” . name calling on issues he doesnt even understand is not exactly scientific nor ethical. better do the research again

  3. More importantly, the funding of studies then inserts a bias into medical education. Lifestyle can work but it requires everyone to go against the ‘grains are great for you, better than any other food including spinach’ mentality the food industry has fostered.

    Patients are screwed. They are forced onto statins by doctors who are fed bad data from Big Pharma–this data has subverted science in a pervasive manner. Then, on the lifestyle side, they are bombarded with ‘grains are great, even highly processed ones that we process to look unprocessed’ marketing that many many physicians and dieticians support.

    This morning I made an egg mcmuffin, the ‘bread’ made out of almond flour and ground flax. 2 tbsp of ground flax have 100% RDA of Omega 3 (of course you need more because there’s so much Omega 6 in our diet). The almond flour lowers LDL, it has fiber and protein, very little carbohydrate, and it lowers the glycemic index of all the foods in the meal. Compare that nutrition profile to a piece of ‘whole wheat’ toast and tell me why we’re pimping flour like it’s crack? Not because it’s nutrient dense. (Source for almond health benefits: http://whfoods.org/genpage.php?tname=foodspice&dbid=20)

    We’re not killing ourselves with bad choices and a poor sense of personal responsibility, it’s homicide by bad science.

    If we can make this big a mistake on statins, what else are we screwing up?

    M

  4. As an “mature’ woman who has been on one statin or another for YEARS and was sceptical when the doctor first prescribed them (and still am, BTW)…thanks for a great post. Do I think that the statins lower my cholesterol? Yes. Do I think that they’ll “save my life”? Considering that all of my maternal female relatives had high cholesterol (went HIGHER on a low cholesterol diet) and lived well into their 90’s…NO!

  5. Science aside, there are a multitude of forums visited by statin victims which depict, in the real theater of patient experience, the horrific toll statins can take on the body. To educate yourself in this area I recommend:
    http://www.spacedoc.com/board/ (read NASA Flight Surgeon) and
    http://stopped_our_statins.webs.com/

    I can tell you from personal experience that statins may reduce your quality of life significantly, and if you are unlucky enough to have a double whammy encoded in your SLCO1B1 gene, the damage incurred may be permanent. Boston Heart Diagnostics has refined a test for this gene variant , link: http://www.bostonheartdiagnostics.com/science_portfolio_statin.php

    Get informed, get well.

    Brooks

  6. the data are available? please, I needed a lawyer to receive ADRs of Lipitor reported to the FDA and then received an almost unintelligeable listing. And in many studies, statistics on specific ADRs were not looked for, and thus absent. here are the numbers in easily understandable format:
    Statin Drugs Given for 5 Years for Heart Disease Prevention (Without Known Heart Disease)

    In Summary, for those who took the statin for 5 years:
    98% saw no benefit
    0% were helped by being saved from death
    1.6% were helped by preventing a heart attack
    0.4% were helped by preventing a stroke
    1.5% were harmed by developing diabetes*
    10% were harmed by muscle damage
    In Other Words:
    None were helped (life saved)
    1 in 60 were helped (preventing heart attack)
    1 in 268 were helped (preventing stroke)
    1 in 67 were harmed (develop diabetes*)
    1 in 10 were harmed (muscle damage)

    Statins Given for 5 Years for Heart Disease Prevention (With Known Heart Disease)

    In Summary, for those who took the statin for 5 years:
    96% saw no benefit
    1.2% were helped by being saved from death
    2.6% were helped by preventing a repeat heart attack
    0.8% were helped by preventing a stroke
    0.6% were harmed by developing diabetes*
    In Other Words:
    1 in 83 were helped (life saved)
    1 in 39 were helped (preventing non-fatal heart attack)
    1 in 125 were helped (preventing stroke)
    1 in 167 were harmed (develop diabetes*)
    http://www.thennt.com/statins-for-heart-disease-prevention-with-known-heart-disease/
    Above posting noted SLCO1B1 variations. The risk alleles present in 26 to 32% of caucasian pop. Studies have noted plasma statin levels of 140 to 400 times normal –toxic levels by anyones estimation.

  7. This post made me really sad. Please take a look at the Lancet’s pieces from August.

    CTT: Primary prevention in 130,000 patients (inclusion: 5yr risk of vascular events < 10%)
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60367-5/fulltext

    JUPITER: Primary prevention and DM risk in 17,000 patients
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61190-8/fulltext

    Editorial:
    Statins for all by the age of 50 years?
    http://www.ncbi.nlm.nih.gov/pubmed/22607823

  8. This post made me really sad. Please take a look at the Lancet’s pieces from August.

    CTT: Primary prevention in 130,000 patients (inclusion: 5yr risk of vascular events < 10%)
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60367-5/fulltext

    JUPITER: Primary prevention and DM risk in 17,000 patients
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61190-8/fulltext

    Editorial:
    Statins for all by the age of 50 years?
    http://www.ncbi.nlm.nih.gov/pubmed/22607823

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