Rob Verkerk PhD, founder, executive and scientific director, ANH-Intl; scientific director, ANH-USA

The statin bubble has burst….supposedly

If you hadn’t noticed that the statin bubble had burst, you were probably suffering a statin-induced fuzzy head and hadn’t managed to stay up with breaking news.

Over the past months a flurry of long-term studies have been emerging, driving the last nails into the coffin of one of the most profitable drug classes the pharmaceutical industry has yet seen. Or so it might seem.

Statins are prescribed for the purpose of reducing cholesterol levels which have long been viewed as a major risk factor for heart disease.

Statin Tablets with Glass of Water
Statin Tablets with Glass of Water

How many people know the long-term risks (or benefits, or otherwise) of statins before they take them?

While the scientific edifice for this assertion may largely have collapsed, major health authorities like the US National Institutes of Health (NIH) are much slower to retract their argument that high cholesterol in the bloodstream leads to clogging up of arteries and increased heart attack risk. This misinformed and greatly over-simplified view results in over-prescription of statins, with the US being the number one prescribing nation in the world and the UK the second biggest. Over a million statin prescriptions are filled each week in the UK.

Heart disease risk: so much more than high LDL

If they were talking about more sensitive measurements of C-Reactive Protein (CRP), sub-clinical low-grade inflammation, apolipoproteins profiles or oxidised fractions of very low-density lipoprotein (ox-VLDL), that would be an entirely different issue. But only doctors and practitioners really prepared to look at the totality of evidence, including emerging evidence, are presently using comprehensive cardiovascular risk profiles including some of these emerging markers. To top if off though, statin drugs themselves actually cause atherosclerosis and heart disease

Pharma won’t give up on statins (and their profits)

Big Pharma, and its servants in health and regulatory authorities, don’t give up so easily. Even the US FDA, while being forced to admit and communicate more evidence of harm, still argues that purported benefits in reducing heart disease outweigh risks, be these kidney, brain, muscle or eye damage, or increased type 2 diabetes incidence. More than that, seemingly outlandish new claims for other ‘spin-off’ benefits keep emerging, helping offset the bad publicity about side effects.

Among the headlines generated recently are:

10 things you really need to know BEFORE considering taking statins

  1. There are over 500 published scientific studies showing harmful or toxic effects of statins
  2. Common side effects include muscle damage, impaired heart muscle function, liver damage, muscle and joint pain, fatigue, impaired brain function, memory and cognition, loss of libido, depression, and reduced circulating levels of key nutrients such as coenzyme Q10, selenium, glutathione, these and other factors contributing to increased risk of atherosclerosis and heart disease
  1. British private health insurer BUPA cites common side-effects of statins as stomach problems – pain, diarrhoea, feeling sick and vomiting, jaundice, headache, sleep disturbances, dizziness, depression and extreme tiredness
  2. Cardiovascular risk is over-predicted by risk calculators used by doctor’s to prescribe statins
  3. There is no compelling evidence to show any benefits of statins for the very elderly, even though these are among the group with highest rate of statin medication
  4. The 2011 Cochrane Review of the evidence from 14 randomised clinical trials (RCTs) showed that only high risk groups might gain some benefit in quality of life, while “Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk”.
  1. Cochrane changed its conclusion with its review in 2014, recommending statins to all those with raised cholesterol, irrespective of risk. This revised conclusion was largely as the result of the influence of one trial headed by leading British statin advocate, Dr Rory Collins that was likely tainted by his Pharma interests. Additionally, Dr Collins has also tried his best, fortunately unsuccessfully, to bury the views of his scientific critics. The Cochrane review also discounts the importance of side effects—contrary to a gamut of evidence and clinical reporting over years, as well as the requirement to warn patients of such risks on product information leaflets.
  1. The evidence that long-term use of statins significantly increases and approximately doubles the risk of type 2 diabetes is unequivocal. Brand new evidence from long-term studies also shows clear evidence that statin use increases the risk of acute and chronic kidney disease.
  2. For those who have a low risk of suffering a heart attack, leading British cardiologist Dr Aseem Malhotra argues that a daily apple will do more to protect the heart than using statins.
  3. Find out how you can reduce your heart attack risk without using statins by leading metabolic cardiologist, Dr Mark Houston, Associate Clinical Professor of Medicine at Vanderbilt University School of Medicine; Director of the Hypertension Institute and Vascular Biology; and Medical Director of the Division of Human Nutrition at Saint Thomas Medical Group, Saint Thomas Hospital in Nashville, Tennessee.

    Learn more

     

    Article by Zoë Harcombe: Cholesterol & heart disease – there is a relationship, but it’s not what you think (2014)

    Buy Book: What your Doctor may NOT Have Told You About Heart Disease” (2012) by Dr Mark Houston

    Watch video (Dr Mark Houston)

    Peer-reviewed article by Merck statin researcher, Dr Jonathan Tobert, about the early, chequered history of statins: “Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors” (2003)

 

Comments

  1. After reading a summary of the bad science that this was put on the market in 1951 on evidence which came from 4 countries, they omitted to include 18 other countries which did not support this theory. Again this came to light in the 70’s when theevidence was re examined. These facts came to light that 8 of the 9 doctors on the panel in 1951had vested interest in the pharmceutical company producing it. I advise clients against taking statins.
    This is all well documented in a book called The French Paradox. Check it out. Many of the people in the mediteranean countries live a happy and long life with high cholesterol………
    Checking for potential heart disease the first test should be the homocysteine test which is a more accurate indicator of potential heart disease.
    So keeping this low helps promote good heart health. To keep it at the premium level of taking Juice Plus Capsules of fruit and vegetables daily helps matain a low Homhcysteine level as proved in a study at Sydney University using only food of fruit and vegetable in capsule form. Further information from the Clinic.

    1. Thanks, Patrick. We’ve linked the Zoë Harcombe article that in turn links to Dr Malcolm Kendrick’s book and much of the historical info about the Seven Seas study, Ancell Keys, etc. But yes, the French Paradox is interesting; there may also be the blue cheese effect on the gut microbiome: http://www.ncbi.nlm.nih.gov/pubmed/22981595

  2. My husband have been taking stations for years,since he’s been taking them he’s got type2 diabetes ,stomach problems ,pain in his muscles,but the GP still give them to him,I also take them only 1 at night and all I’ve had since being on these is terrible pain all over my body.

  3. Rob
    one of my pet hates is statins. Here is an article i wrote some time ago about how they may a 0.9% benefit into 30%. Let me know if you would like more.

    Statin Statistics: Lies and Deception

    Tens of millions of unsuspecting people are prescribed cholesterol-lowering drugs—statins like Pravachol®, Zocor® and Lipitor®—each year at a cost of more than billions of pounds with very little, if any, benefit. In the U.S., some 40 million people currently take statins at a cost of more than $3.00 per pill, more than $1,000 per year, totaling more than $40 billion a year.
    While there are many exaggerated claims and a lot of hype about the benefits of statins, there are also many studies showing no benefits at all. The pro-statin hype is based on the misuse and abuse of statistics. Various independent studies in prestigious, peer-reviewed journals have shown that statin use in primary prevention—that is, to save lives—has minimal or no value in reducing mortality and certainly nothing that is considered anywhere near clinically significant to warrant their widespread use. It does not matter how one manipulates the statistics, the results just aren’t there. In data gathered in 2009 from six trials, a review of the efficacy in lowering the risk of death with statins found virtually no difference between the treatment group and the control group. There are many more of these studies.
    In an independent meta-analysis (when a number of studies are put together to achieve more statistical power) of randomized controlled trials in patients without CVD, statin therapy decreased the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality. Taking statins for a number of years will not reduce mortality: “Primary prevention with statins provides only small and clinically hardly relevant improvement of cardiovascular morbidity/mortality.” “Hardly relevant” means there is virtually no clinical benefit; as the authors of these particular studies are independent, they gain nothing by stating this. Another review found that “current clinical evidence does not demonstrate that titrating lipid therapy (trying to lower cholesterol with statins) to achieve proposed low LDL cholesterol levels is beneficial or safe.” In other words, lowering lipids has no real benefit and has the potential for adverse effects. Following up on this, in a major independent review of studies funded by the Ministry of Health of British Columbia (Canada) on statins and primary prevention, researchers reported that “statins have not been shown to provide an overall health benefit in primary prevention trials.” This is a government report carried out by an independent university yet its findings are still ignored.
    The problem really comes down to vested interests and the abuse of statistics. To overcome the limitations of small studies, vested parties combine many studies into a meta-analysis. The researchers themselves select the studies used in the meta-analysis. A fundamental problem is that researchers with direct links to drug companies have the authority to select the most positive studies and ignore the rest—including independent studies not funded by pharmaceutical companies. Despite this, they have still not been able to show any clinically significant findings.

    With few new studies being conducted, the drug company researchers look at the data every year or so and conduct another meta-analysis to show virtually the same results as the earlier studies. This makes it appear that another big study has been conducted, but frequently the data is simply reused from older studies. There is very little clinical significance in these studies, yet the media outlets pick up the drug companies’ PR and repeat, word for word, the pharmaceutical industry’s party line.
    As readers of the scientific journals, we should not be confused between statistical significance and clinical significance. For an outcome to be “statistically significant” means that the outcome was likely result of the treatment—whether the result was 100% effective or less than 0.1% effective. That is, if you treat 1,000 people to save one life (0.1%) it may be statistically significant but it is not clinically significant. “Clinical significance” means 20% to 30% or more. The drug companies’ most positive studies on statins for prevention of CVD report statistical significance, mostly 1% or less, and none have found any clinical significance.
    Busy medical professionals don’t have time to review the statistics; few of them may be aware of the different ways the statistics are manipulated. A study found that a high number of psychiatrists did not understand the difference between statistical and clinical significance. Consultants, that is the senior psychiatrists, did less well than senior trainees. So if the experienced professionals don’t understand the results of these studies, how do we expect the media or public to understand? The entire situation is also complicated by the comments in abstracts of the studies, in which researchers state the evidence is significant and don’t mention that it is only statistically significant but not clinically significant. The drug companies fund the researchers and authors of most of these studies.

    More deception
    The studies on statins also report “relative risk,” not “absolute risk” or “real risk.” The relative risk reduction is highly misleading,,,. if not deceptive. An example of relative risk is: if you have four people in a study who die in the placebo group (no drug) compared to three people who die in the drug treatment group—that is, four were expected to die but with the drug only three did—then there is a 25% relative risk reduction. However, to get this effect of saving one life you would have to treat 1,000 people and the real risk reduction is 0.1%. Relative risk is like adding 1+1 to get 11 or 2+5 to get 25 or more. How can the pharmaceutical companies and the researchers working for them get away with this? This is probably because (at least in my experience) most people are afraid of statistics.
    In studies by the Medical Research Council dating back to the late 1980s, researchers found that of 1,000 men ranging in age from 35 to 64 who received treatment for mild hypertension over five years, there were six fewer strokes and two fewer cardiovascular events than would be expected., The real risk reduction over five years was 0.9%. Ten years later, a study of Pravachol® was released in the media, with much fanfare, as having a 22% drop (relative risk, not real risk) in mortality. However, when one looks at the numbers and statistics behind the calculations, treating 1,000 middle-aged men who had hypercholesterolemia (high cholesterol) and no evidence of a previous heart attack with pravastatin for five years resulted in seven fewer deaths from cardiovascular causes, and two fewer deaths from other causes than would be expected in the absence of treatment. The real risk reduction, however, was a mere 0.9%, less than 1% or nine lives out of 1,000 when treated for five years. The research was sponsored by Bristol-Myers Squibb Pharmaceutical (West of Scotland Coronary Prevention Study). Conservatively, put another way, researchers treated 1,000 people for five years at a total cost of over $5 million to save seven people from CVD. One might wish to compare this to the cost and efficacy of adopting healthy lifestyle choices.
    In the Heart Protection Study in the United Kingdom, more than 20,000 participants aged 40 to 80 years with high risk of cardiovascular disease but average-to-low levels of total cholesterol and LDL cholesterol were treated with 40mg daily of simvastatin (marketed under several trade names including Zocor®). Of 20,500+ study participants, 577 on statins died from a heart attack, 701 not treated died from a heart attack. That is a 25% relative risk reduction over five years. Sounds good, doesn’t it? An interesting point is that using their statistical method, the researchers got their own claims wrong. The real percentage improvement is actually 1.7%. Over the five-year study, they saved 25 people per year in a high-risk population with previous cerebrovascular disease, peripheral artery disease, renal impairment or diabetes. These are seriously ill people and the researchers still achieved a benefit of only 1.7%. Researchers neglected to mention that around 30,000 people were not allowed in or dropped from the study and not counted in the percentage of people with side effects. There were 10,269 people on statins and 10,267 people on a placebo.
    A study of 90,056 participants combining 14 randomised trials looked at the best outcome for people who had pre-existing conditions: 47% had pre-existing chronic heart disease, 21% had a history of diabetes and 55% a history of hypertension. The death rate was 8.5% among the statin group compared to 9.7% in the control group. This difference represents 1.2%. That is, if you treat 100 people who already have serious pre-existing diseases that predispose them to a heart attack or stroke, you are likely to save 1.2 people. The study made no mention of side effects for all participants.
    The well-known JUPITER study compared a placebo group to a statin-taking group. The study found that there were 68 heart attacks in the placebo group and 31 heart attacks in the drug treatment group—a 58% relative risk reduction. There were 64 strokes in the placebo group, compared to 33 strokes in the treatment group, a relative risk reduction of 48%. Sounds good, doesn’t it? However, the drug treatment group had 8,901 participants in it. In real terms, the heart attack risk went from a very low 0.76% to 0.35% and the risk of stroke went from 0.72% to 0.37%. Effectively, if you treat 300 people with expensive and dangerous drugs you might save one life. Under the best possible scenario, the real risk reduction was well under one half of one percent. The real risk reduction of consuming a handful of raw mixed nuts is much higher. It is interesting to note that one of the risk factors used to select the participants in the study was C- Reactive Protein (CRP), an indicator of inflammation and the real cause of the problem.

    In an independent assessment of the same statistics in 2010 titled “Cholesterol Lowering, Cardiovascular Diseases, and the Rosuvastatin-JUPITER Controversy. A Critical Reappraisal “ by Michel de Lorgeril and her 8 colleagues found that “the JUPITER Study” was severely flawed. This recent analysis did a careful and independent review of both results and methods used in the Jupiter Study and reported that the “trial was flawed”. In an unprecedented attack on the study they (scientist other than myself usually don’t say boo even when it is serious) stated that “The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study.” In other words the big pharmaceutical money influenced the study. And concluded “The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.” This is a scathing attack in scientific terms of the earlier drug company sponsored study. Scientist do not go out of their way to create waves but these ones have not just found different results but also criticised the earlier studies link with pharmaceutical industry. It highlights not only that the studies don’t show any significant results but these studies and the education of our doctors is strongly influenced by the drug companies.

    More recently, a study reported in the BMJ was a meta-analysis of 10 randomized clinical trials of about 70,000 people followed for an average of four years. In these trials, people with risk factors for cardiovascular disease but no history of existing disease were randomized to receive statins or no treatment. The relative risk reduction was 12% for total mortality, 30% for coronary event and 19% for a cerebrovascular event (stroke). However, the real risk reduction was 0.6%, 1.3% and 0.4% respectively. The actual number needed to treat to save one life was 167. Despite this outcome the authors of the study concluded, “In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly (statistical not clinical) improved survival and large (statistical) reductions in the risk of major cardiovascular events.” (“emphasis added.”). In fact, the authors had significant associations with the drug companies and failed to mention it was statistically significant but not clinically significant. Again, busy medical professionals tend to read only the abstracts; claims like this are pretty convincing, though very misleading.
    More telling however, is the latest findings in June 2010 where two major independent studies, one the re analysis of the Jupiter Study reported above and the other “A Meta-analysis of 11 Randomized Controlled Trials Involving 65 229 Participants” (don’t worry about the title) by Ray Kausik and 6 other independent researchers. The study, wait for it, found the use of statins in high-risk individuals was not associated with a statistically significant reduction in mortality. That is, they don’t save lives. Their data combined from 11 studies with 65 229 participants followed for approximately 244 000 person-years, a very big study, reported that this “meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.” In other words they don’t save lives even in a high risk group. Even if you have all the elevated risk factors these drugs don’t work.

    How many more studies to we need to do to show these drugs don’t work?

    Even the economists agree with me
    It is not only the scientists jumping up and down but also the economists are continually questioning the reason for so much statin treatment. In an economic review of statin use, authors reported that it is not cost-effective to treat low-risk people and also stated, “Economic analyses need to increase their transparency to reduce their vulnerability to bias and increase their reproducibility.” A recent study in the U.K. on reducing the cost of coronary heart disease mortality found statins in primary prevention cost £27 828 per life-years gained (LYG), reaching £69 373 per LYG in men aged 35 to 44. That is, to add one year to a person’s life requires spending £69 373 per year. The authors reported, “Amounts of NHS funding are being spent on relatively less cost-effective interventions, such as statins for primary prevention.” There are now dozens of studies like this that pose the same question I am asking: Why are we using these drugs when they are not effective, but you can also add, especially when they have serous side effects?
    The overwhelming outcome of all of these studies, no matter which combination used, even conducted with biases to give the best possible results, is that to possibly save a single life in a high-risk group one has to treat nearly 50 people in a low-risk group. In the population, between 100 and 1,000 people must be treated, with the possibility of dangerous side effects, to potentially save one life. Perhaps we might say that every life is worth that. Indeed, every life is valuable! A nutritional and lifestyle approach can save many lives. Unfortunately the use of statins comes with a high economic price, especially considering that nutrition and lifestyle changes can bring about much greater real benefits and even save money.

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