Yes, if anyone is interested, I enjoyed my holiday. Mountains, snow, skiing, food, France. What more could you ask for?
Whilst away I kept an eyes on a whole series of stories on cholesterol and statins and adverse effects of statins, and suchlike, unfold across various newspapers. Many of you were kind enough to send me said various articles and stories. Some of which were easy to follow. One, in particular, was completely incomprehensible.
HOPE-3, was a study done by Astra Zeneca looking at the use of rosuvastatin vs. placebo. Actually, it was a study done using rosuvastatin alone vs. antihypertensive medication vs. rosuvastatin and antihypertensive medicine vs. double placebo (a term I have never come across before). Double placebo has twice the power of a single placebo? Yes, its ‘Double Placeboman’ playing at a cinema near you.
I have read the HOPE-3 article, and given up several times. I just cannot understand it. Professor Michel de Lorgeril (who ran the Lyon heart health study) also had a go at making it easier to understand. Below is part of his simplification which (I am afraid) is not terribly simple. But it may give you some gist. There is a prize for anyone who gets to his final point:
- No effect on all-cause mortality.
- No effect on cardiovascular mortality.
- As cardiovascular disease is a serial killer, we could conclude that rosuvastatin is shown useless in that trial (as in the previous trials). We could stop the analysis at this point.
- Since the authors do suggest that rosuvastatin was protective, it means that these patients are as “deaths cured”’ or “death prevented”, which is probably not what they expected when taking the pills.
- All this despite the LDL reduction that was close to 30%.
- HOPE 3 investigators curiously examine the effects of rosuvastatin on two “combined primary endpoints” (called “first and second co-primary outcome” as shown on Table 2, below) suggesting that there were two primary hypotheses. This is not “in line” with basic Methods in clinical trial sciences [one trial, one primary hypothesis]. That strange and novel strategy should have been presented long before starting the trial. In any case, the probability of a difference between rosuvastatin and placebo for the first co-primary outcome [the only one to be considered] should have been adapted, a kind of Bonferroni correction; p should have been much lower than 0.05 to be significant; which is not “clinical significance”.
- HOPE 3 investigators present the comparison of rosuvastatin with placebo (Table 2, below) as if there were only two randomized groups. In fact, there were 4 groups as there was a second randomization to test an antihypertensive treatment; and also the combination of cholesterol lowering and blood pressure lowering. In summary, these investigators tested many more than two primary hypotheses. They say that they can pool the data from all the patients taking rosuvastatin (plus antihypertensive) to make the comparison with all the patients taking a placebo, including those taking antihypertensive; thus comparing two groups of about 6300 patients rather than 4 groups of about 3100 patients each) because there was no interaction between treatments. This is not exactly true as we see a clear interaction between treatments for at least two components (myocardial infarction and stroke) of the two co-primary outcomes (see Table S20 in the supplementary materials, below). It would have been therefore imperative to present data and full statistics for the 4 groups together to examine the effects of rosuvastatin vs. placebo. It is a mistake not to do that. 6- HOPE 3 investigator also say that there were fewer heart attacks; but after almost 6 years and with about 13,000 patients randomized, there were only 114 heart attacks (45 vs 69 in a simplistic analysis of 2 groups only, Table 2 below).
- In fact, things are not so clear when looking at Table 2: they report for the first co-primary outcome (CV deaths + myocardial infarction + stroke) 304 events in the placebo group and 235 in the rosuvastatin group, thus numbers different from the sum of 171+69+99 (total 339, placebo group) Michel de Lorgeril 2016 and 154+45+70 (total 269, rosuvastatin) according to the numbers given in Table 2. This means that they do not use the same numbers in the Table and in the statistics. This is a way of misleading the readers.
Ahem. Perhaps not as simple as you may expect, but I hope you get the general drift. All I did, rather than Lorgeril, was attempt to pull out the figures of greatest interest, to me. Which should be the figures of greatest interest to everyone taking rosuvastatin. The absolute difference in number of deaths between those taking rosuvastatin and double placebo.
- After five years of treatment, in 3,181 people taking rosuvastatin, there were 171 deaths (of all causes)
- After five years of taking double strength placebo, in 3,168 people, there were 178 deaths (of all causes)
This represents a difference of 7 deaths over 15,905 years of treatment. Or, one death delayed for every 2,272 years of treatment. This is both statistically, and clinically, insignificant. It is well within the limits of a chance finding. It is a difference that can simply be ignored.
Of course, it was hailed as a triumph, and further proof of the cholesterol hypothesis.
Of more interest, in many ways, and coming out at almost exactly the same time as HOPE-3 was the ACCELERATE trial. Which looked at the use of evacetrapib on lowering LDL (‘bad’ cholesterol), and raising HDL (‘good cholesterol) on the risk of CVD. It was reported thus…
‘Cleveland Clinic researchers studying evacetrapib have shown that despite reducing levels of low-density lipoprotein (LDL, or “bad” cholesterol) by 37 percent and raising levels of high-density lipoprotein (HDL, or “good” cholesterol) by 130 percent, the drug failed to reduce rates of major cardiovascular events, including heart attack, stroke, angina or cardiovascular death.
The phase 3, multi-center clinical trial was discontinued in October 2015, on the recommendation of the independent Data Monitoring Committee after preliminary data suggested the study would not meet its primary endpoint of a reduction in major cardiovascular events. The research is being presented at the American College of Cardiology’s 65th Annual Scientific Session
“Here we have a paradox. The drug more than doubled HDL and lowered LDL levels by as much as many statins, but had no effect on cardiac events,” said Steve Nissen, M.D., chairman of Cardiovascular Medicine at Cleveland Clinic. “These findings illustrate the importance of performing large, high-quality outcome trials. Just looking at the effects a therapy has on cholesterol levels doesn’t always translate into clinical benefits.”
The ACCELERATE trial involved more than 12,000 patients at more than 540 sites who were at high risk for serious cardiovascular problems. They were randomized to receive either 130 milligrams of evacetrapib or a placebo daily, along with standard medical therapy throughout the trial. Study participants either had an acute coronary syndrome 30 days to one year before enrolling, had cerebrovascular atherosclerotic disease, had peripheral vascular disease, or had both diabetes and coronary artery disease.’
In HOPE3, LDL was lowered 30%, had some (very slight) impact on CVD, and was hailed as a triumph for cholesterol lowering. In ACCELERATE LDL was lowered 37%, HDL raised 130%, with no effect whatsoever on CVD. Aha, but, there is an answer…
The ACCELERATE trials was, you’ve guessed it. A paradox. [Question, how many paradoxes can a hypothesis sustain before it collapses in a smoking ruin?]
Karl Popper would call such a thing a black swan. Which is a refutation of your hypothesis. Karl Popper, as we all – ahem – know ‘proposed falsification as a solution to the problem of induction. Popper noticed that although a singular existential statement such as ‘there is a white swan’ cannot be used to affirm a universal statement, it can be used to show that one is false: the singular existential observation of a black swan serves to show that the universal statement ‘all swans are white’ is false—in logic this is called modus tollens. ‘There is a black swan’ implies ‘there is a non-white swan,’ which, in turn, implies ‘there is something that is a swan and that is not white’, hence ‘all swans are white’ is false, because that is the same as ‘there is nothing that is a swan and that is not white’.
One notices a white swan. From this one can conclude:
At least one swan is white.
From this, one may wish to conjecture:
All swans are white.
It is impractical to observe all the swans in the world to verify that they are all white.
Even so, the statement all swans are white is testable by being falsifiable. For, if in testing many swans, the researcher finds a single black swan, then the statement all swans are white would be falsified by the counterexample of the single black swan.’2
Here is another ‘white swan’ hypothesis
Researchers, looking at those living in Framingham, in the US, found that younger men with high cholesterol levels were more likely to die from CVD. From this they concluded. Raised cholesterol causes CVD. ACCELERATE clearly falsifies their simplistic hypothesis. It is a black swan. Thank you, and goodnight.
Next, part XII as to what causes heart disease.
References:
1: http://www.dddmag.com/news/2016/04/evacetrapib-impacts-cholesterol-doesnt-reduce-cardiovascular-events
Dr. Malcolm Kendrick 
“Mountains, snow, skiing, food, France. What more could you ask for?”
Surely, I would ask for a good red wine! It also would be perfect for stabilizing the HPA-axis.
Back to the main issue:
It is best to assume that cholesterol is not the main driver of cardiovascular diseases! This new paradox, adds to the many others that invalidate the cholesterol hypothesis.
Why flooding people with statins on the basis of a flawed hypothesis?
Why not opening eyes and minds such as to search for the real causes of CVD?
You have nailed it. We have wasted at least 4 decades seeking the WRONG basis of CVD. Think of the strides we could have made had we sought the truth… But then, the truth is not what the experts want us to know… it would ruin their reputations
Dr Willcourt,
In a previous blog for which I was too late, I thanked you for your forthright comments. The BMJ is, I believe, trying to remedy this in a series of editorials on views based on “little evidence” but point to the fact that, to quote: “that doctors with dissenting opinions should be heard, but that they may not feel able to speak openly if they fear being struck off (Watkins (doi:10.1136/bmj.i1768)
Completely agree! We lost four decades, millions of lives could have been saved, a huge amount of money has been spent on the purchase of medicines for cholesterol (who benefited?) and most of the medical research keeps ill-directed or even paralyzed by the prevailing dogmas.
That is why I warmly greet people like Dr. Kendrick who continue fighting for a new approach to the problem of cardiovascular diseases
You are so right Dr Willcourt. The conclusions of HOPE 3 made me laugh out loud. Unfortunately, when I read the ACCELERATE I felt a huge sense of frustration. No, Dr Nissan, it’s not a paradox. You are simply barking up the wrong tree. Just come clean and admit it! Your patients deserve no less.
May I correct an error? Of the second trial, we read “the effects a therapy has on cholesterol levels doesn’t always translate into clinical benefits.” I think they meant “the effects a therapy has on cholesterol levels doesn’t even translate into clinical benefits.”
Antonio
Is it not a case of “evidence-based medicine” being flawed by unscrupulous medicine makers fraudulently selecting and interpreting data to suit there own greed? There are unfortunately many examples of this following “the fall of modern medicine” (Dr James LeFanu’s book)
You are quite right, the ethical (and moral) appraisal of the behaviors of many actors in this matter has not yet been openly made.
Talking of paradoxes, you have been skiing in the land of them, where they eat large quantities of saturated fat, have average levels of Cholesterol, and refuse to die.
Quel paradox
Malcolm: reminds me of Pythonesk logic; “halibut are fish, therefore all fish are halibut” 🙂
During the TV show Inside Natures Giants, a scientist noted how clean a whales blood vessels were. Whales eat protein and fat.
Larf for Sunday – white swan v black swan, but height, not versus, just, there can be white, there can be black. Both colours are applicable= nowt set in concrete. Wonder if might get speckled or even piebald ? No matter, wonderful.
Might interest / s’amuse / or even send you clawing at the wall… An article in le Point, a monthly French magazine with on-line daily updates. This was one of the items in a recent on-line – in French, but google will gooleise it for you !
http://www.lepoint.fr/sante/le-risque-d-infarctus-et-d-avc-reduit-grace-a-une-nouvelle-approche-therapeutique-02-04-2016-2029566_40.php
Yep. A ‘new’ approach to treating hypertension – sic :
The risk of heart attack and stroke reduced through a new therapeutic approach
The combination of statins and antihypertensive lowered cardiovascular risk of 30% in all participants of a clinical trial.
SOURCE AFP
Published on 04.02.2016 at 17:10| the Point.fr
Enough to send one into an apoplectic fit…
This is a clinical trial that could change the prevention of heart disease. This is a mixture of drugs against cholesterol and high blood pressure. This new cocktail reduced the cardiovascular risk of 30 to 40%, according to results of a large international clinical trial.
“These findings are incredibly important with a global potential significant impact,” estimated Dr. Salim Yusuf, professor of medicine at McMaster University in Canada, who led the clinical research. The study, called HOPE-3 (Heart Outcomes Prevention Evaluation), was conducted with 12,705 participants in 21 countries for more than five years. She assessed three methods to reduce the risk of heart attack or stroke (stroke) in a population, which while not yet suffering from cardiovascular diseases, presented at least one risk factor, such as excess weight, smoking or family history.
Leading cause of global mortality
According to Dr. Yusuf, “20 to 30 million people could benefit” of this combination therapy in the world. Cardiovascular diseases are the leading cause of death worldwide with 18 million deaths per year resulting from any of 50 million infarction and stroke. These eagerly awaited results were presented on the first day of the annual conference of the American College of Cardiology (ACC) meeting this weekend in Chicago and were also published in the New England Journal of Medicine.
The three approaches discussed have been to treat a group of participants with only medicines against hypertension, another with statins – in this case Crestor from AstraZeneca Group – which reduce cholesterol, and a third cohort with combination of both. In each case, these methods were compared with control groups under placebos. The only statins reduced the risk of heart attack and stroke by 25%. As for treatment against hypertension, they have not reduced the rate of cardiac and stroke among participants, except for those whose blood pressure was excessive.
Finally, the combination of statins and antihypertensive lowered cardiovascular risk of 30% in all participants and 40% in those with high blood pressure. “This clinical trial (HOPE-3) clarifies how to treat hypertension and high cholesterol, two of the most common cardiovascular risk factors,” noted Dr. Eva Lonn, Professor of Medicine, also in McMaster University, and co-lead author of the research. According to her, “primary prevention can be significantly simplified and thus available to most people with an average cardiovascular risk in the world.”
A major impact on medical practice
In industrialized countries where statins and antihypertensive drugs are cheap, “the results of this trial are expected to have a major impact on medical practice,” predicted Dr. Yusuf. These cardiologists also noted that “statins were remarkably safe and beneficial in this clinical trial among all participants whatever their cholesterol, blood pressure, age, gender or ethnicity.” Clinical studies made previously on the combination of statins and antihypertensive were for already sick patients. The HOPE-3 test is the first to evaluate the preventive effects of this cocktail.
Participants in the trial will be followed for a further three to five years. In an editorial published in the New England Journal of Medicine , Dr. William Cushman, professor of preventive medicine at the Veterans Affairs Medical Center in Memphis (Tennessee, south), who was not involved in the clinical trial, believes that these results “come to consolidate the use of statins as an effective preventive treatment against cardiovascular events in this population.” Under the new guide proposed in 2014 by the American College of Cardiology, 56 million men and women with a risk of 7.5% infarction or stroke within ten years, should take statins against 25 million currently.
(For the rest one has to subscribe- I am not a subscriber so info curtailed)
Comments – these are a hoot – gives one pause for…hope
Who funded this study? ?
It is essential to know in detail the funding for this study!
———–
Statins are dangerous. Even more dangerous is this mania for lowering cholesterol levels, even when it is already normal.
These statins crap create pain and annihilate libido.
We Is sure that these doctors are independent of the pharmaceutical industry?
—————
Want cramps
Rusted joints, muscles destroyed? Especially do not forget your statins! The successor of the Pick! You will see.
————
Larf a minute…..(google translated)
Impressive effort to disentangle well hidden nonsense!
This reminds me of the scholastic discourses carried out during the medieval times in order to prove the existence of thing whose existence could not be proven. E.g., no one could disprove the statement that angles exist. Hypothesis which can not be refuted are poor hypothesis to say the least.
Surely they are displaying the non efficacy of said drugs, but some I suppose will rush to have their HDL increased at the very least. May as well take parsley, sage, rosemary and thyme. Fill your pots and grow some herbs. Not to be flippant, it is a serious subject and we have lost a lovely family member with an MI. And I worry about CVA. Hope you are newly energised Dr Kendrick. Long may you blog.
Why do 99% of doctors still subscribe to the cholesterol theory and prescribe statins to their patients? Is it because they never studied logic?
Glad you enjoyed a lovely vacation. Are you a good skier?
Modesty forbids. I started skiing in Scotland where there is nothing to do but try not to get blown off the mountain, and ski on a white substance that occasionally resembles snow. So, most Scottish skiers get pretty good, because the conditions are so bad.
I missed De Lorgeril’s comments on this (I generally keep an eye on his web site). Can you please provide a link.
So glad you got out there and enjoyed some good doctoring.
Kevin
Not sure which one you want but this one is to the point
Journal of Controversies in Biomedical Research 2015; 1(1):67-92.
Doi: http://dx.doi.org/10.15586/jcbmr.2015.11
Can be downloaded in full
Thankfully you came back in one piece.
Even your snow isn’t good snow?
Yes, Dr. Kendrick it is no wonder you are a skillful skier. It is why our poor little country boys who learn to hunt early on make the best marksmen or sharpshooters in the military. As regards Big Pharma, people are beginning to see. People in America are sick and tired of being ploughed with drugs they do not need. There is a huge movement on to see food as medicine once again. In fact, rather than being prescription obsessed, they are now “food obsessed”. They are ditching their anti-depressants, statins, and others by the bucket loads. Big Pharma is running scared because people are on to them. It is common practice in the U.S. for everyone (maybe I am exaggerating a bit) to be told they need an anti-depressant. Almost everyone you talk to who will admit to taking one has been told “you will have to take this anti-depressant the rest of your life”. They are told “You have always been depressed.” Now, how in the world any doctor can make that assessment is beyond me. But, they are told this and find that they can ditch them and eventually find they actually feel better, more productive, and have normal, human emotions as appropriate. What we have is an epidemic of behavioral problems, not medical. And so it goes with statins. If you do those things that help one to avoid the dreaded t2d, get off your arse and get some exercise, get an attitude adjustment, you will do just fine in this world. But pharmaceuticals are huge business. Perhaps, it is time they knew they can’t make such huge profit margins and don’t have to either. Other industries will come about and take their place, and hopefully, people will be better off. I am not anti-pharmaceutical at all. I just think we are over using them and creating illnesses that don’t really exist. I say, move over Big Pharma, there is a new kid in town who wants to try his or her hand at making life better for someone and who is, in fact, honest and decent. Thanks for your insightful blogs, Dr. Kendrick. Just keep chipping away.
You may have two questions there. I just read that in a survey conducted by some organization (which I can’t lay my hands on right now) found that 54% of practicing doctors argee that high levels of cholesterol cause heart disease. However, that may not indicate that they do not prescribe statins to those patients who have high levels. There are other reasons for doing so, especially in the US where litigation is rampant for almost any reason. Most doctors just take the safe route and prescribe.
Precisely. I just had this conversation with my dad who’s been a physician for the last 45 years. He’s anesthesiologist so he doesn’t prescribe statins or anything to patients. But he did tell me that lots of doctors have to prescribe things even if they disagree with it because once a guideline is set, it’s considered to be the ultimate truth. If something happens to a patient, a doc can be sued for malpractice if they didn’t follow what Pharma and KOLs set as a clinical guideline…
Surely the first, and sometimes the only, question to ask about papers is Cui bono? [ “to whose profit?” ]
https://en.wikipedia.org/wiki/Cui_bono
I enjoy your articles. Funny and true.
So do I, Dr Raaste.
Let’s be blunt here. This was an industry-supported trial. We can be confident that they painted the best possible face on it. The statins impressively distorted the fictional LDL-C down by ~30%, but for an insignificant ¼ of 1% improvement in all-cause mortality over 7 years.
That’s appalling leverage, and I wouldn’t be surprised if it vanished or went negative on confirmation (or we learn that the “placebo” wasn’t, and biased those arms). In any event, nearly 700 people died to bring us this pitiful result, many of whom might still be with us, had a strictly dietary intervention been used instead.
As well as placebo does in these trials, I’m sure there is a secret contingent of many, well-funded researchers trying to figure out how the pharma companies can patent placebo. Maybe they are on to something with this “double-placebo” bit? “Hey, Doc! I’ll take a double shot of placebo, over ice, with a twist!”
I have oft wondered what ‘placebos’ may be spiked with. So often the ingredients of a placebo are not given. I understood that a placebo was usually a sugar pill – in a trial on the effects of a diabetes drug for example, the contents of a sugar pill could well skew results.
re: I have oft wondered what ‘placebos’ may be spiked with.
• Sugars, both simple and complex.
• Flours (which might as well be sugars), esp.
• Flours from gluten-bearing grains (numerous adverse components)
• Rice flour (wheat germ agglutinin, arsenic uptake)
• Calcium compounds (an inherent CVD risk factor).
• ω6 PUFA oils, like soybean, heavy in inflammatory linoleic acid
Those are adverse ingredients, which could easily bias a trial arm, esp. over a multi-year study. It’s also possible to cause positive bias. I remarked here that a 2015 paper month was testing fish oil for psychotic disorders and used coconut oil as the “placebo”. CO is very far from brain-neutral.
These things might be “controls”, if their effects are well understood for whatever is being studied, but when they are described as “placebos”, then we know that we are seeing the work of the nutritionally clueless.
It’s actually not an easy thing to craft an adequately blinded and truly effect-free placebo, but when the researchers are nutritionally unaware, it’s much harder (and less likely to have happened).
The lack of any statement about what the placebo was (as in HOPE-3) renders results uncertain. Given what appears to be a total lack of attention to diet in that trial (nothing advised, nothing recorded, nothing useful measured), the odds of not-a-placebo rise considerably.
Personally I liked the reason for terminating early – futile to continue
May be it is futile to continue promoting therapy on the grounds of cholesterol-lowering by any medicine!
Very good
Jut love the idea of ‘Double Placeboman’!
“Just love the idea of ‘Double Placeboman’!”
So do I and it conjured in my mind an image of the Michelin Man (Bibendum) on steroids.
I believe studies found that the combo drug Vytorin (ezetimibe and simvastatin) had results that can be interpreted similarly. Non statin drugs that lower bad cholesterol/raise good, did not change CV or all cause mortality.
By writing in such an obtuse and convoluted way all they are aiming to achieve is for you to give up reading the body of the text altogether, cut to the chase, read and swallow their poorly reached and contrived conclusions. If there was anything of substance in this paper they would make it crystal clear in less than half the space.
By burying the frankly unimpressive results in an ocean of word salad they just hope that their readers will just read the bottom line and come to the conclusion that it’s just another paper confirming the ‘truth’ about the dangers of cholesterol and the wonders of statins. They know that most doctors do not have the time to read through these papers with your tenacity and clarity of thought.
They rely on the fact that statistics is generally poorly taught in medical school and is hardly the subject that medical students rush to the lecture theatre for. It is seen as a boring, irrelevant chore to get through. Start talking in stats lingo, overblow the benefits of said drug by quoting relative risks and downplay the harms by quoting the absolute risks. Do this and you will hoodwink all but the most discerning and critical reader.
When my final years ask me what the most important and relevant subjects to clinical practice are I now tell them that if they know their basic physiology/biochemistry and their stats they should do fine. If they have these nailed then they will have a solid foundation of how the body works (and fails) and will also have the tools to spot the bulls**t in ‘scientific’ papers like this.
Right you are! If there were any significant results, they’d be in the first sentence of the abstract. Then, everything following would be flaunting their p-value and their wonder-drug would be getting a Shkrelian price hike. Whenever the weasel-word-salad is served up, one can be sure there is no statistical and/or real-world substance to the endeavor. WWS – best served with a large side of skepticism.
Back in ~1952-3 my university in their wisdom decided that a course of statistics was essential for vets and I assume medics. Bradford-Hill’s “Statistics for Medical Students” no less. Have used them ever since!
Is there a way to keep track of comments without actually commenting once? Thanks.
Sasha,
I don’t believe there is, which is why I am leaving this.
I would like that too please
You could copy the lt and save them on in a word processor.
re: You could copy the lt and save them on in a word processor.
That’s not the issue. People want to be able to subscribe to threads without having to post gratuitous replies to do so, in order to get email updates on new replies.
Enabling that may or may not be an option in the WordPress template in use (and not being a WP user, that speculation is already more than I know). I’m frankly surprised that we don’t see such empty “ping” responses on many WP blogs with this limitation. In the present case, where pre-moderation is the policy, I doubt any amount of such noise traffic would get approved.
Thanks, I guess it is just easier to say something and have comments coming afterwards. The problem is, there are so many interesting contributions, including yours, that I often have nothing to say. I am learning a lot from this blog, thank you everyone!
If you use Google Chrome then you can add the free rss feed reader here:
https://chrome.google.com/webstore/detail/rss-feed-reader/pnjaodmkngahhkoihejjehlcdlnohgmp?hl=en
You would then follow the main blog page for new blog postings and also follow the comments page for a given blog post.
You would need to add a follow for each new comments page each time a new blog is posted.
It will list any comments as new since last viewing and click on the link to navigate directly to the new comment.
After installing go to the blog page and there is a little plus sign in the top right corner.
Click that and click follow for any feeds available (e.g. comments feed for a given blog post)
Use the gear icon top left to manage settings – how you want the page to open (Open posts in new tab setting turned off for example)
David, thank you for that suggestion.
David, thank you for taking all this effort to explain.
Dr Kendrick,
Thanks for your valiant effort at explaining the results of the HOPE study but they are really easy to understand, if you know where to look 😉 . You probably know of the following article (and I hope I did not miss an earlier reference to it in this blog) but I will post it as it will be of interest to readers who might not know of it.
http://www.jclinepi.com/article/S0895-4356(16)00147-5/fulltext
I am an unconditional admirer of Dr. Ioannidis and this article gives a good idea why. As Canadian I am mortified that the conclusions reached in the study do not survive the test of the most basic elements of mathematical logic and the fact that, of all canadian universties, the study leaders are from McMaster would indicate to me that EBM may be in even greater difficulty than Dr. Ioannidis suggests.
As important as the case of the role of cholesterol/statins in CVDs may be, we know it is only part of a much more far reaching problem.
‘”but had no effect on cardiac events,” said Steve Nissen, M.D’
Is Dr Nissen re-positioning himself here? Perhaps there is some other new drug in the pipeline which we have not even an inkling of?
Wow! Thank you very much for the link, Gilles.
I guess “corruption” is to to hide the obvious and which seems to be the emblem of present day ‘evidence based medicine’.
Dr. Sjöberg:
When we live in a world where a candidate (Sanders) to the US Democratic Presidential candidacy race can declare:
“Wall Street is an entity of unbelievable economic and political power. That’s fact. I want to say something and it may sound harsh, not to you, but to the American people. In my view, the business model of Wall Street is fraud. It’s fraud. I believe that corruption is rampant and the fact that major bank after major bank has reached multi-billion dollar settlements with the United States government, when we have a weak regulatory system tells me that not only did we have to bail them out once, if we don’t start breaking them up, we’ll have to bail them out again. I do not want to see that happen.”,
you can be certain of one thing: corruption is deep and endemic in the business world. At least in part, we see the consequences, in the name of neoliberalism, of ignoring millenniums of human wisdom and handing down the keys of the chicken coop to the fox in the name of efficiency. (I am referring here to self regulating, policing , etc by industry) I will accept the criticism that this reply is culpable of an “excess of perspective” 🙂 but I do believe it is relevant. In the face of such power, logic and prudence will be twisted in whatever shape is required to achieve the desired results.
Gilles
I too am an admirer of Ioannidis’ work and I thank you for the link. There is another PLOS reference (see comment above) which is of value and is/was the most downloaded paper on record.
Gilles, that was a great article (by Ioannidis). He is an excellent writer. Thanks for the link.
Well it may be much worse. In your book, Doctoring , you point out that the incidence of all cause mortality in a statin trial was higher in patients taking statins than the placebo.
The trial you report on here does not mention all-cause mortality. On the basis that screwing around with your bio systems in highly artificial ways generally leads to some nasty results, one has to wonder what the all-cause mortality figures were for this study, and also what the subtle (i.e. not as bad as death but still perhaps bad, like reduced energy, organ damage, etc) impacts of the non-placebo drugs were.
Keep up the good work. Perhaps with your efforts and others we will one day get honest and clinical trials which do not cause harm to pharma victims, er, patients.
Please ignore above remark. All-cause mortality *was* reported, which invalidates the remark above.
I wonder what Dr. Nissen has been smoking. Paradox, that’s funny! Methinks he is protecting future research grants by writing such nonsense. Apparently all three drugs in this class have shown their worthlessness in stage 3 trials. So expect the FDA to fast track them to approval. By the way, interesting things happening on this side of the pond regarding censorship and research fraud. Stay tuned. A sleeping tiger has been awakened.
Which side of the pond are you on?
The U.S. side. Though I’ve just learned a film was recently banned from the London International Film Festival. Our film has been released to theaters, has been well attended, and will be a game-changer.
michael goroncy 15 June 2013 at 3:01 am #
Confessions of a lab rat
In 2005 I joined several thousand others in Pfizer’s CEPT Illuninate study.
Within a short time 2 things happened!
(a) my HDL tripled (marvellous) this is what the trial depended on.
(b) my BP sky-rocketed (mystery) because the side effects were predicted to be marginal and no need for concern)
Up until then, my BP was ‘bobbing along’ nicely in the 110-120/ 70-80..Although having severe CHD, my BP was excellent and never an issue.
Now! For the ‘Circus’ part and it’s management.
My BP shot up to 160-180/ 90/130…not exactly a marginal increase.
I mentioned this to the Cardiac Research Team who were monitoring Lipids, BP and ECG periodically.
I told them I know with absolute certainty that I am in the Trial Arm and not the Control Group…They responded with “You don’t know that”.
Then I dragged my GP (PCP) into the picture and explained this remarkable change in HDL and BP. He was a good, caring GP….and do you know! We spent over a year, adding different Hypertensive drugs and adjusting dosage with no success.
Meanwhile, I am keeping track of Torcetrapib on the net, and can only hear the ‘crowing’ and excitement of this ‘wonder drug’. The closest I could get to any negative..was that the HDL might in fact be a ‘false reading’ (even though the numbers go up- incidence remains the same).
As you all know…Pfizer pulled the plug with extreme haste…when only days before, they could ‘smell the money rolling in’. To me, their noble excuse (a pitiful increase in death with the Combo takers) didn’t equate to flushing hundreds of millions down the toilet. And abandoned their search for the holly grail…and never likely to return down that road. And, even though Steven(rent a quote)Nissen came in to deliver an eloquent eulogy…I have some simple questions to put to Pfizer.
What numbers were they seeing with BP and other markers?
They ‘shat themselves’ for some reason, and I don’t think we will ever know.
For my own experience in this trial…is not open to question.
As for my suspicions…..I stand to be corrected.
Whats your bp now. did you manage to get it back now again. if yes how.
I actually had a ‘event’ while this trial just ended.
My BP had resolved itself within 2 weeks.
Ah, so they’re all ducking for cover because something nasty has been swept under the carpet?
Michael Goroncy
It is called “evidence-based medicine” a much loved and promoted concept; great in principle but its validity depends entirely on an honest and unselected interpretation of the data. This is just not the case (Ioannidis JPA (2005) Why most published research findings are false. PLoS Med 2(8): e124. Downloadable) and many other reports that are simply ignored
CETP inhibitors *COULD* actually be evidence for the cholesterol theory (or it could be evidence that Big Pharma researchers can’t do simple logic). CETP facilites the transfer of cholesterol from HDL to LDL. So they developed a drug to inhibit that. Now you have HDLs that can’t get rid of their load and LDLs that can’t get cholesterol to deliver it to cells that need it. Also the cells that want to get rid of some cholesterol can’t give it to the HDLs. The numbers look great but the system is broken. Maybe the HDL reverse cholesterol transport is not working. Or maybe cholesterol-laden HDL is not as good an anticoagulant. Maybe depleted LDLs do more harm. Maybe depleted LDL gets oxidized more quickly. Who knows? I don’t think anyone will ever look at the problem any time soon. I think they are still trying out new CETP inhibitor drugs.
Hi,
I read the related article by Scott Gavura:
https://www.sciencebasedmedicine.org/statins-for-everyone-not-so-fast
Overall, he has good things to say for Statins:
“Given their unambiguous effectiveness…”
“You “set it and forget it”, and the strategy largely worked”
Can someone please help me understand this better? I’d be very grateful.
I have been a reader of this SBM site for some time. Most of the posts on quackery in medicine are quite good, particularly those by Dr. Gorski. Posts on the subject of nutition (and related such as statins) I find to be interesting but not unbiased. The authors such as Dr. Hall (this is the first I have seen by Scott Gavura) I find to be lacking in objectivity regarding the interpretation of reseach studies and results. What we may look at and say “what a bunch of nonsense”, they are inclined to accept unreservedly. Most of the regurlar commenters on the site (there is a clique of usual suspects) are very intolerant of dissent and actually gang up on anyone who posts dissenting opinions, to the point of rudeness and immaturity. Some of the commenters are medically trained doctors, I believe, and most discount the LCHF diet as a fad that will eventually disappear just like so many other fad diest did. Many of these commenters are statin takers and do seem to be suffering from metabolic syndrome effects, but seem to be uninformed about basic science. When I asked one to show me evidence that eating high levels of saturated fat was harmful, he gave me a link to the nobel lecture given by Drs. Brown and Glodstein on their work in the discovery of the LDL receptor. This reseach did not prove anything related to saturated fat except by implication. Overall, I find the nutrition post on this site to be of very poor calibre considering that it is called Science Based Medicine. As to the other posts on other subjects, they are OK, but it is like preaching to the converted. All the readers know that quackery is quackery and not supported by science, so there is no point in beating this horse. Those who do not have enough science education to know the difference will not be persuaded. Anyway, those are my thoughts. I check the site from time to time, but I rarely post a comment because it is a waste of time.
I should add that Scott may not want to rock the boat by making any suggestions that Statins are not very effective in their function. Dr. Hall is already on record defending the notion that even 1 to 2% is not negligible, and that side effects are rare and mild. However, I an not sure that Scott is reallly defending statins, especially in primary care.
Thanks for explaining.
I’ve read the books by Dr. Malcolm Kendrick. I’m thankful for people like him who have good understanding and can analyze these results. I’m amazed by the amount of disinformation out there.
Can you share any critical thinking sites on health, and other life topics?
(Do you think http://nutritionfacts.org is reliable? I know he is vegan, but appears fairly objective on most things, other than meat related stuff).
Thanks again.
Ndia,
Yes I find Dr. Kendrick’s site to be one of the best. Thank you Dr. Kendrick. Other sites which I frequent and find very credible and science based are Hyperlipid, and Dr. Richard David Feinman’s site, but he does not entertain comments and is not very prolific but he is very science focused. Dr. Mike Eades, Zoe Harcombe, Dr. Ben Goldacre, Dr. Georgia Ede, and Dr. Verner Wheelock. Some of the older sites such as those of Gary Taubes and Dr. Peter Attia are great for review, especially the comment sections, but neither of them are posting any more, it seems. There are plenty more which are good but these are my preferred.
If anyone has some more recommendations, I would be eager to hear them. I personally learn a lot just from intelligent commentary.
I know we are all thinking the same but I have to repeat it out loud while shaking my head: it is truly unbelievable that any trial result that does not fit the cholesterol-CVD hypothesis is labeled a ‘paradox’. Can these ‘scientists’ really hear themselves? Thank you, Dr Kendrick, for educating me enough that I could spot this ridiculousness when I came across it on another site.
Caroline H
I think that Dr Kendrick explained somewhere in his blog or books that “paradox” was a term used by the medical establishment to explain away horrid facts when those facts contradicted the medically “approved Gospel”. The French/Swiss/et al paradox, the obesity paradox are examples where the facts give the lie to official wisdom.
Simple Summary… (In Australia we’d say…) “Bull-dust Baffles Brains” . . . – Works every time 🙂
In truth, the choice of words would be more…’fundemental’ and perhaps anatomically impossible, but you get the drift…
you are dead right on that but then Aussies always tend to call a spade a spade and not some PC approved word
There is only one solution to the problem of Big Pharma’s drug trials.
The medical profession should announce that from now on they will take no account of such trials, but that if a company thinks it has a sufficiently good product, it should put up the money for a trial, over which it will have no control whatsoever! Why the hell wasn’t it set up that way all along?
The current situation is crazy – the doctors will make favourable mention of HOPE-3 to their patients (the name is just so encouraging, and might add some placebo effect) without ever reading it themselves, and in the near certain knowledge that their patients won’t read it either!
The experts will read it, but probably very few will have the courage shown by Dr Kendrick, to announce that even they aren’t clear what if anything it means!
David,
You are of course absolutely right but that is just not going to happen. Big Pharma has too powerful a control of the US Govt and such agencies as the CDC, FDA and the NIH with their revolving door system of researchers. Money and status trumps human health every time; and those docs and consultants at the frontline (who I believe are doing as good as possible within their remit) are controlled by fear of legal suit or negligence charges to buck the system. There is a very strong anti-whistleblowing attitude at the top of the UK medical establishment and the top NHS administration.
Well, We know of at least one doctor who has managed to do a lot of whistleblowing and get away with it so far!
If those doctors who realise there is a problem all stood up and demanded a change it would be awfully hard to resist! I mean they would not be saying “we don’t believe in statins”, but “we can’t rely on medical studies done by drug companies”.
That message would be so simple, and it would resonate with the general public.
David,
There are quite a few that have challenged “official wisdom”. Dr Marcia Angell, Prof. Peter Gotzshe, et al but the hard evidence provided by these skeptics is simply ignored. I must say that “evidence-based medicine” is a gold standard in principle but so many reports are basically flawed through selection, manipulated data and poor interpretation that my faith in this standard is so damaged that I assume, as a first step, that something is wrong and I start looking for errors or contradictory studies – the “paradoxes”and frequently finding them.
Books by David Evans for example identify hundreds of “black swans”
Mike C, can you be more specific re David Evans? I have not found any on Amazon which appeared be relevant.
Mike C, sorry for the Dave Evan query. I don’t know why my search for his books did not show anything, but I have resolved the issue, so please ignore.
“A total of 12,705 persons who adhered to the assigned regimen during the run-in period and did not have an unacceptable level of adverse events were randomly assigned to rosuvastatin (6361 persons) or to placebo (6344 persons).”
How is this even remotely possible? There are 4 groups of which only about a quarter should be in the placebo group, not half! Unless they grouped those who received only antihypertensive in with the placebo group, and the ones given both antihypertensive and statin in the statin group. Either way, by definition, this is not a placebo group as half the data originates from subjects taking an interventional medication (the antihypertensives). And according to the pre-specified exclusion criteria listed before the study was conducted (https://clinicaltrials.gov/ct2/show/NCT00468923 ), subjects on candesartan and hydrochlorothiazide would not have been eligible for the trial to begin with. In other words, including subjects meeting an exclusion criteria in the statistics is dishonest, IMO.
That’s to say nothing about the 4 week run-in phase where subjects were given meds and those who developed adverse events were excluded from the study. But standard practice when statins are involved.
This trial is a complete mess. 1 + 1 = some number that may or may not be two. I work on the general principle that, if you cannot even begin to understand what happened, then something is being hidden
Agreed. I imagine if they conducted the statistics correctly, comparing the 1/4 who took only statins to the 1/4 who took nothing (placebo), statistical significance would likely disappear, or become too murky to spin. Also, the supplementary information does not give the breakdown of the primary efficacy outcomes by individual groups side by side (as in supplemental Table 18 for deaths), but gives you everything else in this format. I smell smoke, and see mirrors.
Science it ain’t.
Stiptec
This study from the the protocol has a smell of the HPS design – a 2*2 factorial design with an initial randomization to rosuvastatin or placebo followed by randomization of rosuvastatin to statin or candesartan and the 2nd randomization of placebo to placebo or candesartan.
This factorial analysis would a result for treat 1, treat 2 and an interaction. Thus if treat 2 and interaction were not significant it would allow the statistical comparison of treat 1 v. placebo . this is what happened in the HPS and as Dr de Lorgeril (Ithink in his book) has pointed out the comparison of statin alone v. placebo has never been published along with the 2*2 factorial analysis.
I hope this explanation helps.
Hi Mike,
Even though it’s been shown, statistically, that there was no treatment effect in any antihypertensive group (that antihypertensives were basically useless in this study), it’s not right to assume that they had no effect at all (they did lower blood pressure significantly, both statistically and clinically, if I recall correctly). The effect on endpoints may not be statistically significant, but there was a small difference. Assuming subjects on antihypertensives “cancel” each other out in the total statistical pool in just plain wrong–eliminating the common denominator. I’m not sure what the term is, since I don’t deal with this type of study design, but I see it as a type of “bio-creep,” where assumed minor differences at some stages do creep up in the final statistics. That’s why all statistics in this study should compare to the 3000 or so subject who received only the placebo and no other study drugs. It’s the only honest way of doing this. They provided safety data in the supplement for this comparison, but did not for the primary endpoints. Very strange indeed.
The problem (with any study using antihypertensives) is that the blood pressure might go down, but to no avail. Most other antyhypertensive drug studies (that I know of, anyway), show little or no benefit for heart disease.
Stiptec
I think your point is pretty much the same as that of de Lorgeril and certainly mine in that the interaction component of a 2*2 factorial is vital as should be known in an institution such as the Oxford CTU. Unfortunately when one starts taking studies apart in detail many fall down as Ioannidis has so clearly demonstrated. My feeling is that until the data of major studies of the infomercial type are available to independent and unconflicted researchers, this problem of “Doctoring Data” will continue.
A thousand thanks, Dr. K. You so deserve that holiday.
This might interest – http://www.agelessnutrition.com/articles/cholest/part0c.html
The Cholesterol Hoax – A Delusion Deludes – Konstantin Monastyrsky
The original essay is in Russian, but google made a reasonable job of translating.
Also, this, which has already been posted here :-
As Monastyrsky says : “CHOLESTEROL REDUCTION HOAX — A DELUSION DELUDES THE DELUDED” : This little “fiasco” proves once again, this time without a shred of a doubt, that the cholesterol reduction charade has been a fraud from the get go. Will it end it? Nope…
Will be interesting to see how long it takes for the many ‘scientists’ involved in pushing the hoax along, to be wiping the proverbial egg off their faces… Hmmmmm. Not to be negative (!) one sincerely *hopes that it will end.
Mec Cham
Thanks for Russian link. I loved the cartoons; and as a review good too.
Mec Cham
Thanks for the links. The Monastyrsky link refers to the biochemistry of cholesterol. If by any chance you understand French and don’t already know of it, you will find the following link fascinating:
A most eloquent exposé, by Pr. Philippe Even, which should leave anyone with a half open mind strongly suspect that the prevailing medical beliefs on CVD are closer to voodoo medicine than to science.
As far as wiping a proverbial egg off one’s face, it would be nothing to them were it not that they are so rich in cholesterol…
The king is dead, long live the king. [Is precisely how long it will take for the new dogma to take over – whatever it turns out to be]
Dr Kendrick,
Maybe I misunderstand your reply and maybe I am hopelessly naive but given that Even is trying to do exactly what you are working so hard at doing – i.e. shedding light on a belief supported by more “paradoxes” than facts – is it not possible to hope that the new dogma (I can concede the use of this word) will be less harmful than the current one and a bit closer to reality? Otherwise, why bother?
On Mon, Apr 11, 2016 at 12:49 PM, Dr. Malcolm Kendrick wrote:
> Dr. Malcolm Kendrick commented: “The king is dead, long live the king. [Is > precisely how long it will take for the new dogma to take over – whatever > it turns out to be]” >
My comment was merely an observation that people very quickly forget the old ‘king’ and immediately support the new king. The king is dead, long live the king. When people say that it is very difficult to get those in power to change their mind, this is not true. Once those in power recognize that the old king is dead (or close to being dead), they switch allegiance very fast indeed. The moment the cholesterol hypothesis looks like being over-turned, the Key Opinion Leaders will be found leading opinion in a completely different direction. Steven Nissen is already signalling (and has been for a couple of years) that the cholesterol hypothesis is, actually, dead. This is merely to confirm his position at the head of whatever hypothesis takes over in future. He is currently standing in places at the same time, deciding when and where to jump.
So, you are confirming that I misunderstood your reply and that I am hopelessly naive. Thanks 🙂
Sometimes I am a bit obscure, I think. My mind jumps about a bit.
“The king is dead, long live the king.”
I’d like to see something more like:
” The old corrupt and stupid king is dead, so let’s take a break to think about how he got to power, and how to stop it happening again!”.
And maybe lets also look at some of the adjacent countries (other bits of dodgy scientific doctrine) to see if three are some more kings that need deposing!
I know human affairs rarely work that way!
“Mountains, snow, skiing, food, France. What more could you ask for?”
I’m off to France soon – I’ll add sun, walking in the hills and far less pollution to that list ! Glad you had a good holiday ! Nice to see you back.
Anne
Hi Malcolm
Why don’t these papers get more airtime or action? Several doctors had a GP journal club discussion on Twitter last night about the de Lorgeril paper. You can find the comments @GPjournalclub
What struck me was that there were no detractors of the paper and no defenders of the status quo as if everyone knows the truth and just shrugs.
The only comment I got today was from a man with familial hypercholesterolaemia who believes statins have saved his life because all the other members of his family died 20 years before him. Can you refer me to a good article about that?
Lately it is only the Key Opinion Leaders I have heard stand up in defense of statins but none of them joined in last night.
Joanne McCormack
@JoanneReynold14
Did you see how the American College of Cardiology responded in spite of no response in the high risk group…
““Low risk patients could be another group of patients that could potentially benefit from this drug, but we didn’t test that and to do so would require an extraordinarily large study that asks a different question from the one our study was designed to address.”
…. let’s waste even more money.
That is an astonishing response! They know which side their bread is buttered on.
Now the link to the article is lost on the Cleveland Clinic Website, hum.
https://my.clevelandclinic.org/about-cleveland-clinic/newsroom/releases-videos-newsletters/2016-4-3-evacetrapib-impacts-cholesterol-but-doesnt-reduce-cardiovascular-events
The Cleveland Clinic has definitely scrubbed it… But a search under the second half of the heading produced a raft of links. Here are a few results :-
Evacetrapib impacts cholesterol but doesn’t reduce …
http://www.eurekalert.org/pub_releases/2016-04/cc-eic033116.php
Apr 3, 2016 – Evacetrapib impacts cholesterol but doesn’t reduce cardiovascular events … many statins, but had no effect on cardiac events,” said Steve Nissen, M.D., … Still, the improvements in cholesterol did not result in any reduction in …
Press Releases – American College of Cardiology
http://www.acc.org/…/evacetrapib-fails-to-reduce-major-adverse-cardiovascula...
Apr 3, 2016 – Evacetrapib Fails to Reduce Major Adverse Cardiovascular Events. Trial discontinued after drug shows no clinical benefit, despite impacts on cholesterol … The favorable effects on cholesterol did not translate into any reduction in the … but we didn’t test that and to do so would require an extraordinarily …
Evacetrapib Fails to Reduce Major Adverse Cardiovascular …
https://www.sciencedaily.com/releases/2016/04/160403200139.htm
Apr 3, 2016 – … a large clinical trial to investigate the cholesterol drug evacetrapib was … it did not reduce rates of major adverse cardiovascular events, according to new research. … it is designed to affect simply has no effect on cardiovascular risk. … but we didn’t test that and to do so would require an extraordinarily …
Evacetrapib impacts cholesterol but doesn’t reduce …
https://scifeeds.com/…/evacetrapib-impacts-cholesterol-but-doesnt-reduce…
Evacetrapib impacts cholesterol but doesn’t reduce cardiovascular events … (HDL, or ‘good’ cholesterol) by 130 percent, the drug failed to reduce rates of major …
Dr Giebel,
First it is great to see another MD commenting..
Second, deleting results that contradict the official line is unfortunately quite frequent. The only thing is that the item frequently turns up elsewhere on the internet. Some examples include the 800,000 deaths consequent on using beta-blockers pre-surgery (in guidelines followed by a cover-up), the CDC and NHBLI congestive heart failure epidemic (https://wayback.archive-it.org/3635/20130901052131/http://library.thinkquest.org/27533/facts.html), WHO-BHF graph of cholesterol level v. death rates ( Estimated lowest mortality rates for TC blood levels
All Cause mortality 222 mg/dl 5.75 mmol/L
Non-communicable disease 210 mg/dl 5.49 mmol/L
Cardiac Disease 208 mg/dl 5.44 mmol/L
http://www.heartstats.org/documents/download.asp?nodeib=6797 This URL no longer exists? WHY?
Now on https://renegadewellness.files.wordpress.com/2011/02/cholesterol-mortality-chart.pdf
http://healthcorrelator.blogspot.co.uk/2009/12/total-cholesterol-and-cardiovascular.html
And so on. There are also those published reports that are simply ignored.
As Dr. S. J. Nichols who led the trial said: “It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?”
— Dr. Stephen J. Nicholls 2016
Source: https://en.wikipedia.org/wiki/Evacetrapib
Keep up the good work Dr. and thank you for your blog.
It can only boggle a mind that has gone on vacation. Perhaps Dr. Nichols has been taking too many statins.
The problem is simple. When statistical association of a surrogate marker is significant, the assumption follows that the surrogate is causal and belief then takes over. This study has finally demonstrated that those beliefs are just wrong. But challenging a KOL does not work – the truth simply becomes a paradox – the KOL cannot be wrong!
See reference 1: “We were certainly hoping for different results…”.
Doesn’t really inspire confidence in the objectivity of the experiment does it?
More of the same here from Professor Michel de Lorgeril
‘A careful examination of the most recent statin RCTs (Table 2), followed by comparing statins to each other, clearly shows that contrary to what has been claimed for decades, statins do not have a significant effect in primary and secondary prevention of cardiovascular disease.’
http://jcbmr.com/index.php/jcbmr/article/view/11/26
It’s such a shame that such a clear and easy to read paper can only get published in such a obscure journal. Can’t possibly be due the conclusions the authors make….
DBM
Treat 3 million and save 10,000 lives a year reduces to an efficacy rate of 1/300% – trivial but the quote sounds wonderful. The HPS was published in the Lancet.
I agree entirely with you.
Just a thought on the risk algorithm, It identifies individual patients with a 10% risk of a cardiac event in 10 years. This “diagnosis” means that 90% of patients will not have a cardiac event in that time but are still at a ~20% risk of adverse reactions,
Furthermore from lifetables for England and Wales (2008). for men aged 65, there is a ~10% chance of death from all causes in the next 10 years; just like the cardiac event risk. I this an overestimate of the risk?
As a retired academic ,if students had presented this to me I would have sent them away to re-do it. It fails to follow the rules of research and fails to provide a proper conclusion. Its like someone making a graph of their results and then turning the graph upside down to make it fit what they want. Some of it is just waffle,used by students to fill in what they don’t know or to fill up the pages..
PS Glad you enjoyed your holiday
I’m thinking of having a summer T shirt printed with
I LOVE CHOLESTEROL on it.
You could sell some along with your books Dr K.
That’s good, in the sun cholesterol is converted into vitamin D. So you get two benefits for the price of one.
I’ve ordered my T shirt and will probably order at least another one if I like it. It has a big red heart for the ‘LOVE’ bit (rather appropriate!) and I’m having it all on the back and front.
There may be amusing aspects to all the nonsense we read but it does make you angry too. So a little militancy can’t go amiss.
My husband and I spend half the year travelling in our motorhome. This year Ireland and France will get to see my T shirt – oh and I shall try not to pass hospitals without making an entrance. Time they see that Joe public has a point of view.
Dr Kendrick
I am a great believer in Vit D3. A pubmed search on “heart failure” & “Vitamin D” produced some interesting recent reports that support its use.
http://www.vitamindcouncil.org has an interesting newsletter on the subject
As many readers here know, LCHF is a very strong grass-root movement i Sweden and unanimously we advocate saturated fat to replace the carbs and shun the omega-6 PUFA vegetable oils. By doing so we have ridiculed the official nutrition academia which constantly claim that “Fat is bad!” and especially the saturated fat which “Will raise the cholesterol!” and for the same reason “PUFA’s are good!”. This is basically the only line of defence and they are not interested in going into any details here since the “Cholesterol is bad!” dogma prevails.
Something has though happened during the last weeks or so. Numerous vicious attacks on LCHF from all corners have now, all of a sudden, appeared in different media. The resistance has off course been there all from the beginning 10 years ago but now we note a different tone.
I am scratching my head wondering why this change. The only thing I can come up with is that since there i no science behind the official recommendations they are not open for any serious arguments and with roughly a quarter of our population now going low carb they cannot officially ignore us any longer but have to attack.
Especially they don’t want to be accused of being “academic quacks” from academic people like me outside their own “Nutritional Fort”
We are a fact!
An annoying fact to say the least!
Hi Dr. Göran Sjöberg and all of you avid readers
I have a 4 year experience with two Swedish programs: Martin Berkhan’s ‘Leangains’ version of intermittent fasting, and Andeas Eenfeldt’s LCHF principles as well as Australian chef Pete Evans Paleo dietary plan. The results are stunning. Fat loss, reversal of abnormal triglyceride to HDL ratios, lowering of oxidized LDL particles, correction of abnormal LFTs…
No one is on a statin, hardly ever need a hypoglycemic as T2D reverses within a few weeks for most people, even becoming ‘undetectable’ for most. The sooner we recognize that the modern Western diet is a catastrophe and demand that changes be made to the gietary guidelines the sooner 80% of us will live a better life.
Well said Goran and Dr Willcourt.
The cracks in the low-fat cholesterol edifice appear almost daily and the upholders of the current orthodoxy are getting desperate. Some are ever so slowly distancing themselves from the old position. Yesterday’s opinion piece in ‘The Times’ by Matt Ridley again exposed the nonsense and praised the work of Gary Taubes and Nina Teicholz. It’s hard to imagine that something like this would have been published even five years ago.
http://www.thetimes.co.uk/tto/opinion/columnists/article4730637.ece
I am afraid that Ancel Keys “7 countries Study” really turned me off. A classical case of selection to get the answer he wanted; combined with the studies by Yudkin that showed that sucrose was a major problem (now flavour of the month) that were simply ignored at the time. Now of course some bright young thing is claiming a “breakthough” in nutrition on this long known fact.
And the combative Keys systematically attacked John Yudkin, who was measured and civilised. I don’t think he was really equipped to deal with someone as ruthless as Keys. According to a recent talk by Gary Taubes, Keys has been receiving funding from the sugar industry since the 1940s. I wonder if any scientific mistake has done more harm than the diet-heart hypothesis? And the supertanker plows on, although it’s rusty and holed.
In our litigious society just imagine the outcome if one obese or class 2 diabetic person succeeded in suing their government / health service for its wrong advice. The courts would be snowed under and countries bankrupted.
Well, Dr Mainstream and prof. Knowitall will tell thee that you don’t understand “feces” (avoiding profanity here) :
The trial was’nt powered to assess all cause mortality. (You idiot! , will they even think )
Go learn some statistics (will they tell thee) !
To this I have 2 replies, but they have eyes , yet they don’t see.
And then they will throw the genetic studies that prove the LDL theory. Like http://www.ncbi.nlm.nih.gov/pubmed/26910273
Good luck !
Lebret
Thanks for the link – interesting. *Is this the first step in a “BS baffles brains” stunt to rejuvenate this daft cholesterol myth, I wonder. I suspect so; cholesterol has been such a wonderful golden goose that BP and its KOLs will try very hard to maintain the money flow!
David Bailey,
I sent you another email, copying your address carefully.
Recently I watched a broadcast of 2008 on tv. They spoke of the IDEAL study. In this study they compared Lipitor 80mg (n=4439) to simvastatine 20mg (n=4449). In the Lipitor group the total number of persons who died where 366 (218 from CVD). In the simvastatine group 374 (223 from CVD) died. LDL levels where lower in the Lipitor group. From these numbers is it safe to say that LDL lowering doesn’t make you live (significantly) longer?
Eugene:
If “patriotism” is prverbially the last refuge of the scoundrel then “paradox” must serve the same function for the bankrupt (imperfect) scientific concept.Paul Helman,M.D. Wilmette, Il
From: Dr. Malcolm Kendrick To: helman_paul@yahoo.com Sent: Sunday, April 10, 2016 11:58 AM Subject: [New post] Lowering cholesterol has no effect on heart disease #yiv6440888843 a:hover {color:red;}#yiv6440888843 a {text-decoration:none;color:#0088cc;}#yiv6440888843 a.yiv6440888843primaryactionlink:link, #yiv6440888843 a.yiv6440888843primaryactionlink:visited {background-color:#2585B2;color:#fff;}#yiv6440888843 a.yiv6440888843primaryactionlink:hover, #yiv6440888843 a.yiv6440888843primaryactionlink:active {background-color:#11729E;color:#fff;}#yiv6440888843 WordPress.com | Dr. Malcolm Kendrick posted: “Yes, if anyone is interested, I enjoyed my holiday. Mountains, snow, skiing, food, France. What more could you ask for?Whilst away I kept an eyes on a whole series of stories on cholesterol and statins and adverse effects of statins, and suchlike, unf” | |
Malcolm, this will not surprise you: Researchers have found another “health paradox”.
Researchers have found that healthy old people have higher blood pressure and higher cholesterol levels: They termed this the “centenarian paradox”.
http://healthydietsandscience.blogspot.co.uk/2016/04/healthy-old-people-have-high-cholesterol.html
Thanks for this. I await the ‘tipping point’
fresh from the Guardian:
http://www.theguardian.com/society/2016/apr/13/replacing-animal-fat-in-diet-may-not-reduce-heart-risk-says-study
Has anyone seen a plausible explanation why PUFA lower cholesterol at all? I have heard some handwaiving arguments, such as that the PUFA are less stiff than a straight saturated fatty acid, hence the cells pull in cholesterol from the bloodstream to stabilize their wiggly membranes, or that PUFAs oxidize easily, so cholelesterol is needed to heal the damage. None of this is quantitative.
NYT article has more facts:
http://well.blogs.nytimes.com/2016/04/13/a-decades-old-study-rediscovered-challenges-advice-on-saturated-fat/?mabReward=A6&moduleDetail=recommendations-0&action=click&contentCollection=Health®ion=Footer&module=WhatsNext&version=WhatsNext&contentID=WhatsNext&src=recg&pgtype=Blogs
Eric,
I like your kind of ‘curiosity’ since I believe that it is on this basic molecular level our homeostasis is established and maintained although the interaction with higher levels is overwhelmingly complex and which is manifest by the incredibly variation of the blood cholesterol level among individuals not least among us belonging to the CVD “community”. This is an irrefutable and well known fact among cardiologist but not among the ‘lay’ GP’s. E.g., I was lucky 1999 when surviving my extremely serious heart attack that my cholesterol levels were so low that they didn’t prescribe any statins.
The grim fact is that we actually don’t know how this intricate homeostatic web works but can only speculate about details in the ‘understanding’.
Since you brought up the cholestrol ‘regulation’ matter on this basic level I cannot refrain from once more posting a remark I made on a previous post on this blog.
—————————
I believe that ‘knowledge’ is possible! This is why I relentlessly keep to my ‘dear’ textbook “THE CELL” (Alberts et al,) where I this very Saturday morning, with wide open eyes, happen to read the following about how our cholesterol levels are ‘regulated’.
Hold on!
It is all about the communication between what is happening in the cytosol and the nucleus in our cells.
“An appropriate stimulus releases the gene regulatory protein from its cytosolic anchor or mask, and it is then transported into the nucleus. One important example is the latent gene regulatory protein that controls the expression of proteins involved in cholesterol metabolism. The protein is made and stored in the ER. When a cell is deprived of cholesterol, the protein is transported to the Golgi apparatus where it encounters specific proteases that cleave of the cytosolic domain, releasing it into the cytosol. This domain is then imported into the nucleus, where it activates the transcription of genes required for both cholesterol uptake and synthesis.”
And this is just a detail of the complex web of physiological reactions involved in the cholesterol regulation.
What scares me here is that with this kind of ‘knowledge’ there are ample possibilities to put a stick somewhere in a running wheel by a ‘well designed’ drug and then sell this drug under the presumption that cholesterol essentially is a ‘bad molecule’. This is exactly where, in my eyes, the corruption and the abuse of true basic science by Big Pharma enters the medical equation.
In my ‘dear book’ I have still not found a single indication that the cholesterol molecule should be fundamentally ‘bad’ so I keep to the book! 🙂
Sorry for supplying the good stuff piece-meal, finally found the study:
http://www.bmj.com/content/353/bmj.i1246
Just goes to prove that massaging and putting spin on trial results to fit preordained hypotheses has been going on for a long time!
Thanks Eric for the link. The conclusions are a very large flock of black swans.
Conclusions
Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.
Eric: Thank you for this. Final nails in the coffin? Not likely. Pharma is nothing if not tenacious.
Eric,
Thanks for pointing this out.
This reemerging study seems to be all around now.
If you have done your homework properly this piece of information fits rather well to unveil a corrupt medical community. I just wonder what they are going to do about it.
There seems to be some desperation around – interesting!
Eric
excess/toxic PUFA are packed into lipid droplets, which inhibits their oxidation and protects the cell. But what then, what is the LDs’ fate? Many possible scenarios: burn for energy (mitochondria or peroxisomes, requires metal activated enzymes) or store (not always good) or hijacked by pathogens as a food source…
Diana, this explains how PUFAs are disposed of, but not how consuming them lowers cholesterol.
Similar, I keep seeing claims that eating saturated fats raises cholesterol, and I seem to remember having seen reasonably credible proof of this, but never an attempt at an explanation. Maybe this is even weirder, as consuming biocompatible saturated fats would lower the requirement of cholesterol for repair work. Truly, animal saturated fats come with cholesterol as part of the bargain, so maybe in that case the extra cholesterol is simply ingested (but then the de novo generation should be regulated down). I have seen this claim of raised cholesterol levels also for palm and coconut oils, which do not come with cholesterol, but I am not aware of any studies proving this.
Yet another study shows that lowering cholesterol has no effect:
http://www.dailymail.co.uk/health/article-3536942/Ditching-butter-veg-oil-not-better-heart-Fresh-research-finds-drop-cholesterol-no-effect-risk-heart-disease-death.html
“Fresh research has cast further doubt on the guidelines. Scientists from the US’s National Institutes of Health found those who ate more of the ‘healthy’ fats in vegetable oils saw their cholesterol fall.
But this improvement in cholesterol did not translate into a drop in heart disease or risk of death compared to those who ate butter.
In fact, those with the greatest reduction in their cholesterol levels appeared to have a higher risk of death, the study, published last night in the British Medical Journal, found.”
Here is best dietary heart health advice. 1. eat food you like 2. don’t stress 3. eat fresh foods in moderation 4. limit sugar 5. don’t measure cholesterol 6. take some exercise…. Of course nobody will pay me for this advice.
Dr Kendrick – you said that there would ‘probably’ be a new pusch on the drug front… – here ya go –
https://www.sciencedaily.com/releases/2016/04/160419083902.htm
New hope for treating atheriosclerosis
Date:
April 19, 2016
Source:
The Norwegian University of Science and Technology (NTNU)
Summary:
An American mother’s hunch might result in new treatments for patients who can’t tolerate conventional cholesterol-lowering drugs.
We’ll see where this one takes em –
And another little snip from the latest ScienceDaily –
Compound from hops lowers cholesterol, blood sugar and weight gain
Posted: 19 Apr 2016 05:18 AM PDT
A recent study has identified specific intake levels of xanthohumol, a natural flavonoid found in hops, that significantly improved some of the underlying markers of metabolic syndrome in laboratory animals and also reduced weight gain.
They are quite *determined to continue with the cholesterol thesis…
What about people who have Familial hypercholesterolemia (FH)? Has lowering their cholesterol an effect on heart disease?