A long awaited study – the Enhance study – indicates that the combination medicine Vytorin not only doesn’t stop the growth of plaque but may actually increase it, which isn’t particularly pleasing to Merck and Schering-Plough, the pharmaceutical giants that make the drug.
We’ve all seen the annoying commercials ad naseum. Cholesterol comes from two sources: Fettuccine Alfredo and your grandfather, Alfredo. The various people from whom you’ve allegedly inherited your tendency are dressed in outfits that kind of match the look of the foods that cause your cholesterol to increase. If you’ve been lucky enough to have avoided these ads, I’ve included one at the bottom of this post so that you can be as annoyed as the rest of us. I never watch TV other than the occasional football game (or in the case of this past weekend, every NFL playoff game), and I’ve seen the Vytorin commercials countless times. I’m sure it’s one of the most heavily run ads on TV.
Vytorin is a combination of Zocor (simvastatin), the first statin drug approved, and Zetia (ezetimibe), an inhibitor of cholesterol absorption from the GI tract. It is expensive and gives Merck, the maker of Zocor, a way to continue harvesting loads of money from a drug that has now gone off patent and is available as a generic.
Results of the Enhance study have been withheld for some time now giving critics of the drug industry cause for claiming that the companies involved were fiddling with the results to make them more to their liking. Meanwhile millions of people are taking Vytorin while God only knows how much money is being spent promoting it.
Now, as reported in a front page story in today’s New York Times, the results are in, and they are disastrous.

The Enhance trial was meant to prove that Vytorin’s combination of Zetia and Zocor would reduce the growth of fatty plaque in the arteries more than Zocor alone. Instead, the plaque actually grew almost twice as fast in patients taking the combination.
Reducing plaque growth is crucial, because plaque formation — known as atherosclerosis — can lead to the blockages and blood clots that cause heart attacks and strokes, said Dr. Howard N. Hodis, a cardiologist at the University of Southern California. That is why the trial’s finding is worrisome, Dr. Hodis said.

Indeed. I’m glad I’m not one of the 5 million people who are taking Vytorin.
The article contains a statement from a cardiologist at the Cleveland Clinic, a hotbed of statinators if there ever was one.

Dr. Steven E. Nissen, the chairman of cardiology at the Cleveland Clinic, said the results were “shocking.”
“This is as bad a result for the drug as anybody could have feared,” said Dr. Nissen, a widely published researcher and senior consulting editor to the Journal of the American College of Cardiology. Millions of patients may be taking a drug that does not benefit them, raising their risk of heart attacks and exposing them to potential side effects, he said. Patients should not be given prescriptions for Zetia unless all other cholesterol drugs have failed, he said.

Like the statinator of the deepest dye that he is, Dr. Nissen neglected to mention the name of the the statin drug Zocor that makes up the other half of Vytorin.
Another statinator weighs in with a difference of opinion:

Dr. Michael Davidson, a cardiologist in Chicago who has conducted clinical trials of Zetia for Merck and Schering, said the Enhance results did not necessarily mean the drug did not work. Many of the patients in the trial may have been on statins for many years before the trial began, so adding Zetia may have had only marginal benefits compared with its use in a population not as extensively treated for cholesterol, he said.
Still, he said, patients should generally receive a statin before getting Zetia.

Hmm. I’ll bet he does. But let me get this straight. The study shows an increase in plaque, the very condition one hopes would be prevented by the drug therapy under evaluation, and this guy says the results “did not necessarily mean the drug did not work”?
The really tough thing for the statinators and other worshipers at the alter of the lipid hypothesis to come to grips with is that the Enhance study showed that those subjects taking Vytorin reduced their LDL-cholesterol by 40 percent more than those taking the statin alone ( 58% drop on Vytorin – 41% drop on Zocor), yet plaque increased in the subjects on Vytorin. But do you hear any head scratching over this? Anyone saying, ‘whoa there, a lower cholesterol equals more plaque’? Any body at all (other than yours truly, of course) seizing on the obvious? Nope. Not a one. The cry of the herd is ‘back to statins alone.’
Maybe it’s just me, but I would like to think that if I believed with all my heart that LDL-cholesterol caused plaque formation, and then a study came along showing a huge decrease in LDL-cholesterol accompanied by an increase in plaque formation, that my faith might be a little bit shaken. But not so with the statinators.
I posted a week or so ago about a study showing that a low-carb diet acted on the same place in the enzymatic pathway that produces cholesterol as the statin drugs do, but without the side effects. If you really fear LDL-cholesterol, why not treat it with a low-carb diet instead of turning to drugs that can often turn on you? It’s never made sense to me.
For those of you fortunate enough to have missed the Vytorin commercials, here is one for your viewing pleasure. As you watch, ponder on the message in this ad that was beamed to hundreds of millions of people while those PBs (poor bast**ds) on the Vytorin study were having their plaque grow. Kind of creepy.


  1. I read what apparently passes for journalism in the local Tampa Tribune and laughed at poor big pharma. I was surprised to see it published. I wrote apparently because then I read your post and it included a bunch of stuff more damning in the study. Now I’m just mad as usual. Oh well the only time it affects my blood pressure is when I get into an argument with some idiot. Usually a trainer, nutritionist or doctor (not you of course).
    I’ve had knee surgery at the Cleveland Clinic in my rugby days. Glad I don’t get my medical advice there also.

  2. My Mom is on Vytorin. Any idea where I can get a scientific-looking link to email to her about this? Thank you.
    Hi Elle–
    Just Google the words ‘enhance’ and ‘vytorin’ and you’ll get hundreds of hits. Pick the one you think would be most persuasive and send it along to your mother. Or send them all if you really want to overwhelm her.

  3. G’day Mike,
    Thanks for the blog again. I am a type 1 diabetic. Despite great improvements in my day to day life since going on a low carb diet (less than 30 grams a day) my sugar levels are not perfect. I would range from about 4 mmols to about 10 daily, which is much better than 1.5 to 20+ which used to happen on a daily occasion on the high carb diet recommended by my dietician. But I no longer fear daily hypos and feel 100% better. My cholesterol is high according to doctors but my HDL has gone way up and triglycerides way down.
    I’m telling you all this because I have been reading ‘Good Calories, Bad Calories’ and noted that the combo of high cholesterol and high sugar levels is very atherogenic. The increase sugar in the blood somehow encourages the LDL into the walls of arteries?
    I am hardly getting any carbs from my diet but I probably have higher sugar levels than the average person, despite my best efforts at controlling this disease. Could it be that I am therefore putting myself at greater risk by eating a high fat diet and having higher cholesterol levels? Would it almost make sense to reduce fat and increase carbs, even a little? Or even take statins to reduce my LDL? Do diabetics have to do things a little differently to the non-diabetic population?
    Hope this makes sense. Thanks very much for the blog. (I am also interested in high dose Vit D3 tabs and would like to be able to order them from your site. Can’t get them anywhere in Aus.)
    Hi Clint–
    I can’t comment specifically in your case because you’re not my patient, and other than the brief history you gave, I know nothing about you or your condition.
    The sugar circulating in the blood of a type I diabetic is a little different than what Taubes was talking about. If you increase your intake of carbs, then you will actually make more triglycerides and more VLDL in the liver. Just having elevated blood sugars isn’t the same as running a ton of dietary carb through your liver.
    If you are a type I diabetic and your sugars are running high, I would say that you need to manage your insulin dosages a little better. I certainly wouldn’t increase my carb intake.
    Get a copy of Dr. Richard Bernstein’s latest book, and you can learn from well-controlled type I diabetic just how to manage the condition.

  4. Ugh, I hate those Vytorin ads only a hair less than the Lipitor/Jarvik ones.
    The phrase “hotbed of statinators ” is pretty amusing. I’ll have to remember that one as hubby’s health care system is also one from the looks of it.
    I hate the Vytorin ones more because for whatever reason I seem to be drawn to watch them whereas the lipitor commercials I can totally ignore.

  5. I can understand why drug companies push bogus medications. After all, there’s some serious money to be made. But why aren’t the insurance companies fighting it like mad pitbulls? You would think insurers would scour the earth looking for ways to duck and dodge payments for Vytorin and all the rest. They sure don’t shy away from telling doctors and patients what to do in all sorts of other contexts. Now they have a chance to do some good and where are they?
    Hi Ed–
    I’ve often wondered the same thing. But these companies seem more than willing to belly up to the bar for all these drugs all the time.

  6. Hi Mike,
    It’s been a while… again… Thanks for the commentary on the study on Vytorin. Just tonight, on my way home, I happened to listened to a cardiologist commenting on such study. It was disappointing to listen that instead of realizing how dangerous and ineffective statin drugs are to prevent plaque formation, the good doctor said that the question the study ‘attempted’ to answer has nothing to do with the actual purpose of prescribing the drugs. So, paraphrasing the doctor interviewed on NPR, while it is true that the study showed no lowering effect on LDL and an increase in plaque formation, it didn’t show anything with respect to heart attacks, which he kept referring to as ‘events’. So, in his opinion, people shouldn’t stop taking their statins based on the results of this study because the durgs are prescribe to reduce heart attacks, not necessarily to lower cholesterol ‘only’. Statins, according to him, are still the first option to keep his and other cardiologists’ patients away from heart attack. Go figure!
    I missed the name of the doctor and I’m having trouble opening the webpage of Chicago Public Radio to get the exact quote.
    By the way, I didn’t have a chance before but I hope you had a great holiday and a great beginning of the New Year.
    Hey Gabe–
    Happy New Year to you, too.
    Actually the study did show a major lowering of LDL (about 40% more than with statins alone) along with an increase in plaque formation. Also, the group on Vytorin experienced more cardiac events than did those on statins alone, despite the lowered LDL levels.
    Go figure, indeed.

  7. My question is what could make a cholesterol level go WAY up when one eats less than 30 carbs a day. I’ve been following PP for many years … cholesterol always in a range that was acceptable to me (total ranging from 165 to 225 depending it seemed on the fiber I would add, HDL 95 – 130, tiglycerides 35-45, insulin less than 2, and results of the VAP showed LDL in the a/b mid range). Recently I decided to reduce my body fat which I did (lost 13 pounds and went from 22% to 15% body fat) by reducing carbs (intervention level or less) … made sure I got enough fat to keep me satisfied, very very clean diet, lots of high intensity exercise. In other words, I’m going along thinking everything is great and I find out my cholesterol shot up to 417 (HDL 126, Trig. 52,LDL size pattern A).
    My doctor is freaking out … what makes cholesterol go up when it is definitely not carbs? The meat I eat is all grass fed, and I eat virtually no processed foods. Just looking for what my next move will be to keep the doc from trying to give me these drugs.
    Hi Donna–
    Any doctor who would prescribe a statin drug to someone who has a type A LDL-cholesterol particle size distribution, an HDL-cholesterol level of 126 mg/dl along with triglycerides in the 52 mg/dl range should, in my opinion, have his/her head examined. These people should know better than to focus solely on total cholesterol. If the total cholesterol is the only focus, why do they even bother to get the other lab parameters? Yeesh. If you’re really concerned, get an EBT scan to see your calcium score. If it is -as I would expect it to be – in the zero range, you shouldn’t have anything to worry about.

  8. Notice that the enhance sudy was in 2002. Wonder how many billions they made before telling us it was bad?
    At 5,000,000 patients taking the drug times $3.00 per dose over 5 years – it calculates out to a whole lot.

  9. I understand that statins have a very negative long-term effect on the liver, is that true?
    In a number of people they do have negative long-term (and short term) effects up to and including death.

  10. Hi Dr. Mike.
    I apologize that this post is off-topic, but I wanted to run something past you.
    In doing some research on effective surgeries for obstructive sleep apnea (OSA), I found that Maxillomandibular Advancement (MMA) along with Genioglossus Advancement (tongue advancement) has the highest success rates in treating OSA. These procedures comprise the highly effective parts of the “Stanford Protocol” and reach cure rates of 90%. In short, they work by positioning the tongue forward and out of the airway.
    So I got to thinking, “how the heck did Dr.Eades manage to have such success in treating his patient’s apnea with only a low-carb diet?” And why was I NOT having a similar success with LC? I lost weight, but my apnea is still severe, along with a moderately high BP (~140/90).
    A few hours worth of internet research yielded the following tidbits of information:
    (Note: I am in no way a medical professional and have plagiarized everything that follows.)
    1. Increased insulin levels are associated with increased cortisone levels.
    -Cortisone acts as a physiological antagonist to insulin by decreasing glycogenesis (formation of glycogen) and promotes breakdown of lipids (lipolysis), and proteins, and mobilization of extrahepatic amino acids and ketone bodies.
    2. Increased cortisol levels suppress serotonin.
    3. Seratonin keeps the genioglossus (tongue) muscles from relaxing and obstructing the airway during sleep.
    -Exogenous serotonin at the hypoglossal motor nucleus (HMN) stimulates genioglossus (GG) muscle activity.
    Therefore, a LC diet reduces insulin levels, which reduces cortisol levels, which allows seratonin levels to go back to normal, which stimulates the tongue muscles during sleep, keeping it from relaxing and obstructing the airway!
    This also explains why LC hasn’t helped my apnea. I’ve been highly stressed for at least 2 full years dealing with unemployment and financial problems/nightmares while my young children scream & cry and generally act their ages. (Things are getting better, though.)
    Could you please tell me if I’m on the right track, or if I’ve missed or convoluted anything here? I sure hope this is it. Not that any of this is new, but I’d love to hear your take on this. Sleep apnea is pretty bad when you can’t tolerate a CPAP.
    Hi Rick–
    Interesting idea on the cascade of effects. And at first blush it sounds plausible. I haven’t thought a lot about the physiology of OSA because all my patients who have had it got better on the LC diet without any other treatment. But, as with any kind of medical therapy, nothing works for everyone. It’s just so happened that in the set of patients I’ve seen, LC has worked for everyone.
    Your idea could be tested by taking 100 mg 5-hydroxytryptophan (5-HTP) around dinner time. 5-HTP is a precursor of serotonin and is often used with varying degrees of success in place of such serotonin reuptake inhibitors as Prozac, Zoloft and others. If I were trying this I would make sure I got my 5-HTP from a good source to ensure that it really contained the 100 mg of 5-HTP. More often than you would imagine discount supplements don’t contain the amounts of active ingredient that is listed. Which is one of the reasons dealing with supplements is so difficult for healthcare practitioners. You’ll recommend a nutritional supplement to a patient only to be told by that patient that he/she has taken that supplement already without success. Then you as the practitioner don’t know if the supplement the patient took was lousy of if it simply didn’t work. The one nice thing about pharmaceuticals is that the dosages are at least standardized. If you buy 20 mg lipitor pills, you know you’re getting 20 mg of lipitor.
    Sleep apnea is nothing to be trifled with. It is more than just a miserable night’s sleep and fatigue the next day. People can have arrhythmias and die, which is what happened to my best friend (a physician) 11 years ago.
    Keep me posted. And make sure you get your condition treated.

  11. Awesome and important post once again Dr. Eades. Sorry, but I can’t bear to watch the video again.
    Glad you enjoyed it. The post, not the video.

  12. Excellent blog, as usual! But now I have the stupid theme music from Vytorin stuck in my head!!! And I WISH I could ignore the Jarvik ads, but ever since I read someone syaing he looked like an escapee from the old Planet of the Apes series, I just cannot look away…….Ahhhhhh!
    Thanks for keeping us all informed!

  13. Please comment on a situation like this.
    I was on a LC diet but my total cholesterol was 300 to 400. I was in a lipid study and went up to 80 mg of Zocor. Result: Nada. Cholesterol still about 300.
    I suggested this might be because I wasn’t on a low-fat diet, so I was getting enough cholesterol from the diet and didn’t need to synthesize much, so a drug that reduced synthesis wouldn’t do much. They just shrugged.
    Then Zetia came out and I tried that. Total cholesterol came down to something like 250. Then I added a statin and total came down to about 150. HDL stays pretty constant at 50 to 60.
    I agree with you that we don’t really know if high LDL levels will cause heart attacks.
    But the standard conclusion from the Vytorin study, “Start with a statin because the Zetia won’t have any additional benefit” doesn’t make sense for someone like me, for whom the statin had no benefit on cholesterol whatsoever. It might have reduced inflammation, but then why not just take aspirin or Salsalate?
    Hi Gretchen–
    In this study Vytorin unquestionably brought LDL down better than statins alone. In fact, it reduced LDL 40 percent more than statins alone. But to what end? Plaque continued to grow and there were actually more events (read: heart problems) with the Vytorin despite the lower cholesterol.

  14. “The study shows an increase in plaque, the very condition one hopes would be prevented by the drug therapy under evaluation, and this guy says the results ‘did not necessarily mean the drug did not work’?”
    This reminds me of the philosophy of Geoffrey Rose. If it shows a small benefit for a small group of people, then perhaps in a large population there will be a big benefit. Now that’s all fine and good until you get to the “increased plague despite lower LDL” part. That’s the head shaker. I wonder how small and dense those particles are now!
    Or it could be the anti-Rose…if it shows a small amount of harm in a small group of people (as this study seems to imply), then that could extrapolate to a large amount of harm in a large group of people.

  15. “Dr. Michael Davidson, a cardiologist in Chicago who has conducted clinical trials of Zetia for Merck and Schering, said the Enhance results did not necessarily mean the drug did not work. Many of the patients in the trial may have been on statins for many years before the trial began, so adding Zetia may have had only marginal benefits compared with its use in a population not as extensively treated for cholesterol, he said.”
    As the average LDL at the start was 318 mg/dl, it is not likely that they were on statins before the trial. Statins are very good at lowering LDL.
    These were not your average people. The subjects in this trial all had familial hyperlipidemia, so it’s probable that they did have elevated LDLs despite being on a statin. If I were trying to defend this trial, I would say that all this proves is that Vytorin shouldn’t be used by people with familial hyperlipidemia, which, when you get right down to it, is all the study showed.

  16. Unbelievable!! So lowering cholesterol lead to an increase in plaque and the answer from the cardiologists is to keep taking statins to lower cholesterol. I thought doctors were supposed to be some of our brightest bulbs. Why are they so wedded to the lipid hypothesis?
    Sometimes this scenario seems to have come right out of Monty Python!

  17. I love this part of the first quotation:
    “Patients should not be given prescriptions for Zetia unless all other cholesterol drugs have failed.”
    So, what he’s saying is that if the patient has not improved with other drugs, let’s give him this one, which will make the plaque grow almost twice as fast.
    If that’s the kind of logic they’re using, heaven help us all.
    PS: THANK YOU for getting my archives list back! And thanks for considering a “List of LC-Friendly Docs.” (BTW, know any in Maine? Mine’s more LC-tolerant than LC-friendly, but he’s always eager to listen to what I have to say, so I guess I’m good for now. Still . . .)

  18. Dr. E
    Might make you feel better that the business community is as full of disinformation as the medical community. Just read that Fred Hassan’s lieutenant and Schering President Carri Cox managed to dump $28 million worth of SGP stock last year as they tried to massage the results into something not so awful. and failed.
    Unbelievable. Or maybe not. Management knows that an ongoing clinical trial is going badly and dumps stock before the results are released to the public. If true, this smacks of a Sam Waksal (the CEO of ImClone who tipped Martha Stewart off that the stock was going to crater when bad news became public. He’s now doing time.) kind of deal. Wonder if the outcome will be the same.

  19. I found it simultaneously amusing and highly annoying that this particular issue was blasted all over the press, but the fact that statins do not decrease mortality (in most cases) was not. This seemed like an ideal time to bring that up. My speculation is that most people just read abstracts, where authors are know “bend” the truth a bit in support of their pet hypotheses. No abstract from someone associated with a large pharma group is going to say “statinex does not reduce mortality”. Instead, we get “statinex lowers cholesterol”. I am hoping this point will come out in the next few weeks, but am not optimistic. Perhaps a letter to the editor of my local newspaper…
    Hey Damien–
    It actually has started to come out. It’s been a bad week for the statin promoters.

  20. Doc, any biological explanation as to why the plaque increased two-fold? tia
    Don’t have a clue. It does seem to indicate, though, that plaque growth doesn’t have a lot to do with LDL since the LDL levels of those on Vytorin dropped about 40% more than those on just the statin. So, lower LDL equals more plaque in this study. Kind of puts a stick in the eye of the lipid hypothesis of heart disease.

  21. All the conflicting information out there is really confusing. After reading your blog about the ENHANCE study, which questions the benefits of reducing cholesterol, I read about a study that reported substantial reductions in mortality and heart attacks in diabetics who take statins. There was a 9% reduction in mortality for every 1 mmol/l reduction in cholesterol, and doctors were advised to put ALL diabetic patients on these drugs. There seems to be “evidence” out there that will support just about whatever position one chooses to take. It puts patients who rely on their doctors for well-informed advice on a hiding to nothing. I guess I am fortunate that I don’t NEED to use any drugs (apart from insulin) and can be just an interested observer – long may it last!
    Hi Mark–
    I’m in the same boat, i.e, I’m just an observer. But it’s still frustrating to see all this idiocy and greed running rampant. The new full-page ads in the New York Times and other publications encouraging patients not to give up their Vytorin just because one study came out showing some problems. If a single study had come out showing benefit, these same folks would be taking out full-page ads touting it to the heavens.

  22. Here is Schering-Plough’s original press release regarding the ezetimibe phase III results:
    It appears this drug was approved based solely on its cholesterol-lowering effects, without any evidence of an improvement in cardiac endpoints. In addition to the drop in LDL-C, they reported that HDL-C, Apo B, and Lp(A) all improved significantly.
    So these latest results suggest that the current thinking on atherogenesis is completely misguided, even among those who reject the significance of TC and LDL-C.
    Amazingly, as of this writing, Google indicates that no one has yet coined the term “Zetia paradox:”
    Hey Damon–
    Now that I’ve gotten around to posting this comment of yours, maybe Google will pick it up as the Zetia Paradox.
    And I agree – today’s thinking is totally off the mark as it concerns atherogenesis. Maybe the Zetia fiasco (Paradox?) and the attendant negative publicity will start some people inching toward sanity on this subject.
    Thanks for writing.

  23. I just had to know how much these corporate bast**ds were making off unsuspecting people while sitting on the study’s findings. So I calculated the gross receipts for Vytorin using the $3 per day cost and 5,000,000 people over five years.
    It works out to $1,095 per person for one year, adding up to $5,475 per person over the five year period. The total is just shocking and disgusting: $27,375,000,000. For a drug that doesn’t work and in fact seemingly makes the health problems it’s supposed to solve worse.
    Fraud doesn’t even begin to cover it in my opinion.
    My father’s on a statin. I’ve forwarded him information about statins and suggested he talk to his doctor about them and that he consider taking CoQ10 as a supplement, if he decides to continue the statin. Despite all that information, his doctor convinced him that (a) he should stay on the statins and (b) he doesn’t need CoQ10. GRR! But at least my dad’s too cheap to take Vytorin — he’s on one of the generic simvastatins.
    Thanks for posting on this, Dr. Eades.
    My pleasure. Sorry you couldn’t get your dad to take CoQ10 and sorry his doc is such a bozo as to tell him he doesn’t need it.
    Good luck.

  24. Another off topic question, Dr Mike. I ordered the Thorne Magnesium Citramate from your website. (Thank you for such a reasonable price) Anyway, I’m not sure how many capsules to take.
    It says on the label, 150mg magnesium, 300mg malic acid. Is that a total of 450mg, or do I need to take more to equal my daily requirement?
    As you can see, I spend a good deal of time being confused.
    Hi Miriam–
    It’s the magnesium number that counts, so to get 300 mg of magnesium you would have to take two capsules.

  25. Just a quick note that CBS is airing a report tomorrow night on Statins and whether or not they are as effective as the drug companies say they are…should be interesting.
    Thanks for providing such useful information…
    Hey Liz–
    I’m a few days late and a few dollars short of getting this comment up in time. I hope many got to see the CBS report – I didn’t.

  26. You’re drawn to watch those ads b/c they *are* funny! It’s cute how they can make people look like the food right next to them, no? At least I think so.

  27. This is for Rick,
    Be sure to get your thyroid levels checked out by an endocrinologist (not as easy as it seems as there is controversy over the lab reference ranges, primary docs often don’t understand thyroids well enough, etc.). Sleep apnea is a not-as-well-known symptom of hypothyroidism. The muscles of the soft palate are too weak from the hypothyroidism and collapse during sleep.
    After I finally got proper treatment for hypthyroidism, my strange “coughing fits” that used to wake me up repeatedly had ceased. My husband was the one who made the connection. I had always assumed the “coughing fits” were some sort of allergic post-nasal drip (probably due to guilt about not dusting often enough – LOL), as I have none of the usual Sleep Apnea risk factors – my BMI is about 21-22, I sleep with my mouth closed, and I don’t snore. But it comes back a bit in the autumn, when I feel like my “gas tank” is on empty again and I need a seasonal thyroid hormone adjustment.
    You never know.

  28. The only problem with all the whining about this study is whether the results can be extrapolated to the general population who don’t have rare genetic conditions whose
    mechanism of cholesterol production you would not expect Zetia to stop since Zetia works in the gut to reduce absorption of cholesterol in food and probably bile acids. For this group yes increasing simvastatin alone would probably be the better choice but can we extrapolate this study to all. All doctors who use Vytorin have seen dramatic results of this drug in their everyday cholesterol lowered patients. Big Pharma constantly shoots them selves in the foot by studying inappropriate groups with their drug then are saddened and start back peddling and delaying release of this study. The study designer should be fired for stupidity.
    I think that the people who continue to say that the lower the cholesterol the better should be shot for stupidity.
    And you are of course correct in your statement that studies in people with genetic abnormalities should not be extrapolated into the population at large.

  29. Sir q for you oot the blue.After one loses the fat on a low carb diet after some years it seems many put on a fair proportion of the original fat loss.I think yr mucka Gary T said something like this on Larry King-Dong.
    So do you think if you are low carbing and thus perhaps low cal-ing to some degree ones body is more primed to store any excess ?
    Any thoughts about dat pleasum ?
    Hi Simon–
    There has been a lot of work done on this phenomenon known as adaptive thermogenesis, which indicates that it is indeed more difficult to maintain after weight loss than the calories in/calories out theory would imply. I plan a post on this in the near future as a part of my Anthony Colpo disciplinary process.
    Stay tuned.

  30. Can you comment on this one in a new blog posting?
    Benefit of Low-Fat Over Low-Carbohydrate Diet on Endothelial Health in Obesity
    Hi Jari–
    I’ve pulled the paper, but I haven’t had a chance to read it critically yet. I will, however, and if it is decent, I’ll post on it.
    Thanks for the heads up.

  31. Hi Doc,
    Just curious why this instance has been picked up on. Three studies, two are bad
    one is good, Gee which one shall we publish. ? We know this goes on constantly but now it
    is getting seriously looked at by our fickle media. I really find it rather funny that the folks I
    talk to are horrified that a drug company could get away with this. I guess I am sliding of into
    the “cynical chasm” but when I mention that this is pretty much SOP people look at me like
    I am from the moon. Is there any real hope that this could signal a change Dr Mike, or as usual will this be last weeks news next week. thoughts ?
    Hey Michael–
    We can only hope. I think all the negative press of the last week may make a few people sit up and take notice. Unfortunately, most of the negative articles were in the business press whereas the defensive arguments were in the medical press. But who knows? Maybe some sanity will prevail.

  32. I am certainly not medically qualified, but I am reading the Gary Taubes book.. it is not easy reading, but I am sticking with it. I thought something he says about the size of the LDL particles might explain why lowering cholestrol (even LDL going down) may not help with plaque in the arteries. I think I understood that lowering cholestrol (eg. with statins) especially while still on the so-called ‘healthy’ high carb/ lowfat diet will actually lead to lower good HDL and lower LDL. However lower LDL in this case will actually lead to higher amount of much smaller sized and more harmful VLDL particles … a double whammy of lower HDL and higher VLDL … Could this be why we have more risk of plaques with statins in combination with the ‘healthy’ high carb/ lowfat diet?
    Anyway, I am I glad I stopped taking Lipitor a couple of months ago … my doctor still thinks that they are great ‘like drano … keeps things clean’. I love my eggs and eat my steak. I think I will take my chances … thank you very much.
    Everytime there is a TV ad on anything to do with diabetes or heart disease, my teen agers laugh because they have seen my before/ after results and understand that low carb is probably the only real way for type2. They now understand how to eat, unlike me at their age. So, something has been accomplished.
    Statinators … I read this as Stalinators the first time around… Wonder why?!
    Stalinators, indeed. I do wonder why?
    I suspect you’re on the money with why there was more plaque on the Vytorin group. But, we’ve got to remember that these subjects had an underlying genetic disease causing them to produce way more cholesterol than normal, so whatever happens to them doesn’t necessarily apply to the rest of the populace.

  33. I really enjoy your blogs. Thank you. With 4S, LIPID, HPS studies on statins ( http://www.rxfiles.ca/acrobat/cht-lipid%20agents-major%20trials.pdf ) trials showing reduced mortality in secondary prevention, is there still no room in your arsenal to prescribe these?
    Hey Busy–
    This says exactly what I wrote in my post a while back. Statins have been shown to bring about some slight reduction in all cause mortality in men under the age of 65 with established heart disease. Were I such a person or if I had one in my practice I might consider a statin drug only after I had tried every dietary and supplement regimen I could put together without effect.

  34. I keep getting these types of [junk] emails. Who is this Blaylock, do you know, Doc? SOME of what is in the email seems on track, but . . .
    Russell Blaylock is a neurosurgeon in private practice and on the staff at the University of Mississippi. He wrote a book titled Excitoxins: the Taste that Kills about aspartame, MSG and other ‘excitotoxins.’ Other than his book, the premise of which I think is a little overblown, I don’t know much about his other opinions.

  35. Following up on the other Rick’s comment, in your experience, how long does it take for a low carb diet to alleviate apnea? I’ve been low carbing for a month. I hope I’m not one of those guys for which it doesn’t work.
    Hi Rick–
    Based on my experience with a number of patients, it works fairly quickly. Usually within a week or two. But that doesn’t mean that diligent adherence for longer won’t ultimately help.

  36. Today there’s a report about drug companies not publishing or skewing results of drug trials that show that anti-depressants are ineffective. The pharmaceutical industry is beginning to make the tobacco industry look good.

  37. I found another article, this time from Gene Emery (Reuters), that popped up on AOL’s ‘news’ page: “Data on Antidepressants Often Shelved.” This one’s about anti-depressants specifically, but it’d be easy to extrapolate to any other drug that pharmaceutical manufacturers are trying to push.
    The article finds that not only are studies that prove the drug ineffective not published, some are even ‘spun’ to make it APPEAR that the results show that the drug is effective, when the data really shows that it isn’t. It also mentioned that unpublished studies account for nearly a third of all the studies done, at least for anti-depressants.
    Yep, it came from a New England Journal of Medicine article that I’m going to post on.

  38. Hi Dr. Mike,
    I’m new to low-carb – seven weeks in – and even newer to your blog. I do however find it quite packed with super useful info. The whole atmosphere at this site is extremely friendly, and I have become almost addicted to visiting and browsing at least an hour or so a day (almost … who am I kidding?).
    On that note I stumbled upon a post of yours from 10. August 2005: Weight Loss Maintainance, where you tell about the infamous James O. Hill and his White Paper at sugar.org – the one he pulled probably in order not to look like a darn fool. You linked to the Google-cached version of this version, but that alas is also lost now.
    For the convenience of your blogreaders, you had copied most of the “paper” and put it up as Sugar White Paper. Only trouble is that O. Hill in a pinch could claim that it was a fabrication of yours made solely to discredit him. Well, maybe not, but it would be futile of him anyway – you see, the White Paper is still out there!
    That’s right – there is a thing called the internet archive at archive.org. They save most of the internet year by year – they must have a server the size of Manhattan – and lo and behold – the James O. Hill sugar rant is locked away in their vaults.
    And to enjoy for all eternity!
    Kind regards,
    Hey Michael–
    Thanks for the kind words.
    And thanks for the link. Now he can live on in infamy for all eternity.

  39. Dr Mike,
    I know you said not to ask medical questions, but will you answer a supplement question? I hope so. It’s so hard to know what to do. One could easily be swallowing 100 pills a day, I think. Based on your comments about how important these nutrients are, each day I take:
    2 tsp Carlson’s Fish Oil
    20,000 IU Vitamin D3 gelcaps
    400 mg Mg Glycinate
    Is there anything else I should add or change/increase/decrease?
    I’m a 43 year old healthy female, mother of 3 young children, and follow a LC diet. I’m at a good weight. I reside in Northern VA.
    If you can’t answer, I understand. I’m just confused about supplements…as usual.
    Hi Elle–
    I would be careful taking 20,000 IU of vitamin D3 daily without checking a blood vitamin D level (ask for a 25(OH)vit D level). You can get too much, especially if you’re taking the cod liver oil as well. Get a blood test and take enough vit D3 to keep you in the normal range. Click here for everything you ever wanted to know about vitamin D.

  40. What a bunch of crap. The drugs companies can poison the world and get rich. One expert said this means you should not take any drug that has not been on the market for at least 7 years, since you can’t count on their so -called “research.”
    I hope Cox goes to prison.
    You may get your wish.

  41. Dr. Mike: thanks again for your sharp eye and great insights on this topic.
    Dr. Howard Brody also had an interesting post about the “Enhance” study today on his blog. I’ll paste just the intro and you and your other readers can check out the complete commentary if you like:
    * * * *
    Wednesday, January 16, 2008
    Now That We’ve Been ENHANCED–What’s the Message?
    Since I last blogged about the ENHANCE trial:
    …the big news of the week, that I’m a couple of days late commenting on, is the mind-numbing flop of the ENHANCE trial. When Merck and Schering-Plough started to do the usual Pharma tapdance, specifically calling in an expert consultant group to change the trial’s endpoints before the results were announced (without the supposed principal investigator even being at the meeting), we all started to predict that the study results were not favorable to the companies’ drug, and that skullduggery was afoot to re-spin the results to somehow make the sow’s ear look like a silk purse. Few of us guessed just HOW totally disastrous the results actually were, as finally revealed this week– that the drug ezetimibe (Zetia), added to a statin (as in the combination drug Vytorin), not only failed to improve arterial wall plaque in any demonstrable way, but may even have worsened it.
    * * * *
    By the time I got to the end of Dr. Brody’s commentary I was cheering because I think maybe the mainstream is starting to get it. Tiny, incremental steps maybe….but they’re finally beginning to get it. (Or maybe I’m just the naive, pollyanna type.)
    Cheers and Best Wishes,
    Hey Wil–
    Thanks for the link. And sorry it took me so long to get it up.

  42. Hey Mike,
    I have been following this a little more closely than I otherwise might because as you know I got drawn into a debate with Dr David Sullivan, “a specialist at Sydney’s Royal Prince Alfred Hospital and the (Australian) Heart Foundation’s spokesman on cholesterol” whose comment on ENHANCE I’ll post for anyone else interested in the sort of contortions apparently necessary when you are a “spokesman on cholesterol” these days”
    He says:

    The ENHANCE trial was an attempt to use a second type of medication, which boosts the cholesterol-lowering effect of statins to see if it could improve the appearance of carotid arteries on ultrasound scans (this is regarded as a “surrogate” for cardiovascular disease) – a test that can be done more quickly on a smaller number of people in the hope that it will be consistent with the disease process itself). Current knowledge led us to expect that the medication would improve the appearance, but there was no difference from treatment with statins only. *This goes against the “lower is better” philosophy behind cholesterol treatment, so it does give us pause for thought.* Whilst there was no evidence of benefit, neither was there any evidence of harm – any small differences between the groups were insignificant. It would not be unusual for a larger programme that was designed to study the number of heart attacks and strokes to show that the same treatment could be beneficial. Those studies are under way and most of us feel that we should wait until those results are available before we alter our approach.

    One of the things that concerns me most about this issue is that there has yet to be any interest from any news outlet in this country – and considering the number of people who must be taking these drugs here …
    But your press and it seems congressmen are a little more concerned, as this piece in Newsweek shows – http://www.newsweek.com/id/94969
    Apart from the amusing reference to the obvious (but thankfully doomed) attempt to “put lipstick on this pig” two things don’t quite gel. One (of the many) excuses for the long (almost 2 year) delay in publication was apparently that “the data was biologically implausible”!!- we should certainly pause to consider that one! – but contrast that with the claim that Carri Cox is in the clear because “These trades go back to the spring of 2007 and the data for this trial were only unblinded about two weeks ago”. Well I’d say they can’t have it both ways – either they have been scratching their heads about “biologically implausible data” for two years or it was “unblinded” two weeks ago … because surely until it was unblinded no one could tell how “plausible” it was?
    Hey Malcolm–
    It is amazing to see the contortions. We have a relatively small study that shows no benefit, so therefore we need a larger study that could possibly show some benefit. Crazy. You could just as easily say that we need a larger study because it might show more damage. Yeesh.
    And the what-did-they-know-and-when-did-they-know-it scenario is also beyond belief.

  43. Ok – I don’t see that this study demonstrated anything other than an elaborate waste of money to demonstrate absolutely nothing.
    They measured IMT changes in a bunch of folks all treating their cholesterol numbers.
    Baseline mean for Vytorin group 0.68mm – after 2 years treatment mean = 0.6911mm
    Baseline mean for Zocor group 0.69mm – after 2 years treatment mean = 0.6958mm
    Baseline mean for no treatment ??? after 2 years no treatment ??? unknown
    mean IMT for Zocor group after 2 yrs 0.0047mm > Vytorin group
    Can anyone point me to a study that establishes any clinical significance to a change of 1/2 of a thousanth of a mm in an IMT measurement? Can anyone point me to a study that establishes the acceptable SD for the measurement of IMT?
    Sorry – but for me this study was snake oil from the very beginning.
    Hi Labrat–
    It demonstrated that a very expensive drug taken for 2 years didn’t do squat in terms of treating that which is was prescribed for.

  44. You said, “In this study Vytorin unquestionably brought LDL down better than statins alone.” My point was that there are people in whom STATINS ALONE DO NOTHING.
    Hence their choice is total cholesterol levels over 400 or taking something like Zetia.
    So the logic that they should just take a statin doesn’t apply to them. No one is addressing the problems of this population.
    Whether or not a microscopic difference in plaque, with a poor P value, assuming that artery thickness is, indeed, directly related to plaque, means anything in terms of cardiac events remains to be seen. It’s my understanding that it’s unstable plaque that is the problem.
    The CV events, although larger (something like 2 events instead of 1) were suggestive but not statistically significant.
    I am committed to LC, as I think it has a lot of other benefits, especially for a person with diabetes. But someone needs to address the problems of those in whom LC alone is not sufficient to reduce astronomical cholesterol levels.
    Even if you don’t believe in the cholesterol hypothesis when cholesterol levels are in a highish range, we know that people with really astronomical levels in familial hypercholesterolemia do often die from heart attacks in their 20s. Therefore, it can’t be totally irrelevant.
    Hey Gretchen–
    The data indicates that people with familial hypercholesterolemia (FH) do indeed die at greater rates from heart disease than do those without the disorder, although not to as great an extent as might be imagined. But people with FH also die a little less frequently from other diseases, namely cancer, as compared to those without FH. Overall, in terms of all cause mortality there really isn’t much difference – if any – in those with FH and those without.
    I suppose then that it would be an individual choice as to whether or not pursue cholesterol lowering at all costs verses just leaving it alone.

  45. Is it possible that Vytorin reduced cholesterol without reducing apo-B so that in effect it reduced the size of the LDL and hence increased plaque?
    Did they measure apo-B?
    Could be. I don’t know if they measured apoB or not. As far as I know this study isn’t available in printed form. All I know about it is what the drug companies released in their press releases. I would like to see the actual study. If anyone comes across it, send it my way.

  46. Did you ever notice that more Jarvik lowers his cholesterol, the more he looks like Gollum.
    Hey Razwell–
    Good observation. Maybe you’re on to something.

  47. Dr. Mike, Can it be said that this study just proves our point about low cholesterol? Regardless of how it gets lowered, low LDL levels and small particles will always increase plaque? Am I coming to an conclusion that is not supported by these particular datum or is it something being completely overlooked? Did they bother to look at why the plaque increased, was it something related to the medication or a result of the lower cholesterol?
    Hey Dave–
    I don’t know that anyone really knows at this point why the plaque increased. And remember, although the plaque almost doubled, the change didn’t reach the level of statistical significance. We’ll have to see a lot more data to figure out what really went on hear. Another thing to remember is that these subjects were not normal subjects with high cholesterol levels, but were subjects who had familial hypercholesterolemia, a genetic disorder. Whatever happened to these subjects can’t necessarily be extrapolated to what would happen to subjects without this genetic disorder.

  48. I used to love those commercials. Forget the content, they had striking visuals that got the message (two sources of cholesterol: genes and food) across very cleanly. I think they’re only really annoying with repetition. I haven’t tracked formally, but find a high concentration during football, the nightly news and other things that tend to draw a lot of middle aged and older men to viewing. When I watch the NBA, much lower incidence of Vytorin ads and very few of Dr. Jarvik from the Forbidden Zone on the PotApes. Law and Order, in reruns, tends to have a lower density of these ads (and ED ads) as well.
    Quick question: Recently, saw an ED ad (I am immature, I find any ad where a man comes on and talks about his inability to rise to the occasion amusing, even if they are all actors) that targets people with diabetes and high blood pressure. If you have these conditions, apparently, you’re more liable to go on TV and brag about your difficulties. Or at least have difficulties. But, fortunately for you, there is ED Drug X (I can’t remember which one it is that’s plugging with this commercial… maybe the one with the bathtubs). Now, on to the question:
    Perhaps a growth opportunity for PP/PPLP/The Next Book would be to tout it as a cure for ED. Since diabetes and high blood pressure are associated with ED, perhaps the best treatment for both would be the best treatment for ED.
    Just a thought.
    Last thing: given the media buying prerogatives of statin merchants, perhaps the cure is to watch less football.

  49. Hello Mike,
    Thanks for the article. I’ve been on Vytorin for 2 years, and was on Zocor prior to that for several years. Last week, I requested that my cardiologist prescribe something other than Vytorin for me.
    I just checked my mail order prescription center to find that he prescribed Vytorin AGAIN! How can I convince my cardiologist that I am not comfortable continuing with Vytorin and that I want to return to Zocor or some other alternative?
    Do you believe that continuing on Vytorin could be risky?
    This is a call you’re going to have to make with your own physician. I can’t give you medical advice over the internet.

  50. Dr. Mike
    MISREPRESENTING the data in the ENHANCE trial . I am NOT for the Lipid Hypothesis but atherosclerosis did NOT increase.
    There was no benefit from an LDL reduction of 58 % but the plaque did NOT increase.
    That NY Times article is incorrect.
    Hey Razwell–
    Actually you are correct, sort of. Plaque did increase, just not significantly. The amazing thing, however, for believers in the lipid hypothesis is that it didn’t DEcrease markedly. An element of the lipid hypothesis is the notion that elevated LDL increases plaque formation and reducing LDL decreases plaque formation. In the ACCORD study we have a situation in which a substantial reduction in LDL concentration not only didn’t reduce plaque, but actually increased it (although not to a statistically significant level).
    The NY Times article wasn’t incorrect because there was an increase in plaque in the subjects taking Vytorin. Where they were wrong is in not reporting it as a non-statistically-significant increase in plaque. (I’m assuming the Times didn’t do that – I didn’t actually go back and read the article again.)

  51. Dr. Eades
    Cholesterol Theory proponents are now saying that the median LDL level of 134 mg/dl in the study was not low enough for any atherosclerotic plaque regression . They say you need to have LDL levels 100 mg/dl.
    The study was flawed they say.
    I know this is nonsense though.
    Nonsense to the max.

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