Friday, December 21, 2007

Patients and Physicians should BOYCOTT Zetia and Vytorin: Forcing MRK and SGP to come clean with the data

You wouldn't believe it - or would you? The NYT reports today that SGP has data from a number of - go figure - unpublished studies that may contain important data about increased [and previously undisclosed] risks of liver toxicity with Zetia and Vytorin: Unproven benefits, undisclosed risks? If I were a patient, I would want to be taken off this drug and be put on atorvastatin or simvastatin or a similar agent. If teh medical community would get on board and take patients off of this unproven and perhaps risky drug, that might at least force the companies to come clean with their data.

In fact, I'm astonished at the medical community's reluctance to challenge the status quo which is represented by widespread use of drugs such as this and Avandia, for which there is no proof of efficacy save for surrogate endpoints, and for which there is evidence of harm. These drugs are not good bets unless alternatives do not exist, and of course they do. I am astonished in my pulmonary clinic to see many patients referred for dyspnea, with a history of heart disease and/or cardiomyopathy who remain on Avandia. Apparently, protean dyspnea is not a sufficient wake-up call to change the diabetes management of a patient who is receiving an agent of unproven efficacy and which is known to cause fluid retention and CHF. This just goes to show how effective pharmaceutical marketing campaigns are, how out-of-control things have become, and how non-normative physicians' approach to the data are.

The profit motive impels them forward. The evidence does not support the agents proffered. Evidence of harm is available. Alternatives exist. Why aren't physicians taking patients off drugs such as vioxx, avandia, zetia, and vytorin, and using alternative agents until the confusion is resolved?


  1. Dear Dr. Aberegg,

    I respectfully disagree, at least in part, with your attack on the failure of the corporate sponsors to publish data on Zetia.

    First and foremost, I submit that we do not have all of the information required to reach make a judgement. An accusation by the New York Times falls fall short of our requirement. This article makes repeated references to "unpublished studies." Importantly, the article indicates that the studies were not registered with clinical

    A key purpose of clinical is to prospectively identify all trials so that a company cannot cherry pick certain trials to present. If a company cjooses to exclude studies from the registry, the sponsor is precluded from using the information garnered in this study to support registration.

    Additionally, we do not know the nature of these studies. Were these safety 'studies' (which are really longitudinal, observational cohorts of patients taking drug required by the FDA for approval). Were these placebo-controlled studies? Were these meta analyses?

    There remain many unaswered questions about ezetemibe, and the long-term benefit and risk profiles are paramount among them. However, I feel fairly comfortable with the conclusion that Zetia lowers LDL by 15-20%. I am comfortable allwong physicians to make clinical judgements as to whether they believe affecting this surrogate marker to this degree is clinically menaingful.

    Unfortunately, there is often a limit to the amount of information that can be gleaned in clinical trials. It is only after years of expereince that we grow to fully undertsand the risks or benefits that therapies truly confer. Statins are a good example of this. These were approved on the basis of LDL lowering and have subsequently been shown to have marked clinical benefits. Avandia, as you point out, is another example. This drug was approved on the basis of lowering Hgb A1c. It now appears that the benefits of the drug (in my opnion) do not outweigh the risk. As for Zetia, the jury is still out.

    Because the long-term profile is not known, it is not an unreasonable course for you to boycott Zetia from your clinical armamentarium. However, I submit that it is not unreasonable for other physicians to make their own decisions.

    If you then counter that prescribers do not have the full data set to make an informed decision, I would continue to respond that we simply do not know if this is true. There has been a large volume of data on Zetia that has been presented or published. I am not willing to make the leap that the studies referenced by the NY Times are of any relevance (I am not even sure if they are what we would really deem to be 'studies.')

    Finally, I would note that these data have been submitted to the FDA (the NY TImes identified these studies from FDA briefing documents). While I do not consider the FDA a final arbiter of data, I take at least some comfort in knowing that the data have been vetted (and are not locked away in a corporate vault to never be seen by persons outside of the corporate umbrella).

    Despite my disgareement with your conclusion, I admire and respect your drive to protect the integrity of data and the welfare of patients. I appreciate your thought-provoking blogs and look forward to future additions.

    Dr Michael Bernard
    New York

  2. Dear Dr. Bernard: Thank you for your thoughtful comments, which serve to temper my perhaps too-galvanized opinion on this topic.

    I will only add that as physicians, knowing that companies are driven by profit as much as by pursuit of the truth, that we have the right to demand forthrightness, candor, and transparency from these companies, as our patients entrust us as the gatekeepers of these medicines. When companies like MRK and SGP are not transparent and obfuscate when important questions are asked, especially when they have a history of prior transgressions (Vioxx), we should refuse to use their products until they come clean with full disclosure. This is our only apparent leverage with these companies, who ultimately depend upon us to prescribe their agents.
    I am not basing the call for a boycott on concerns of safety alone - I am partly calling for it to exact transparency from these companies who may or may not be trustworthy as regards what is best for patients.

  3. It is *far* past time physicians quit acting as an employee of industry and began to stand for their patients. But no worry. We aren't waiting on this (having been burned oh I've lost count how many ways and times in conflict of interest and selective trial reporting). We aren't accepting those prescriptions anymore, and further, we are working hard to educate other patients.

    Consumers: keep your eyes on the NYTimes. Note also that much of the Canadian Medical Association journal, the New England Journal of Medicine, the British Journal of Medicine, and all of open access journal PLoS is available to the common man and women online. Go to and drop statins AND adverse effects into the go bar. Do the same in Google: Lipitor AND adverse effects, Lipitor AND peripheral neuropathy, statins AND Beatrice Golomb, statins and James Wright also all in Google. You can also find courses online on how to read and understand medical studies. Know that most articles touting some new drug or treatment, have been bought and paif for by pharma. There's good golf that day.

  4. My 14-year-old daughter has familial hypercholesterolemia. She is on lovastatin, and her cardiologist wants to add ezetimibe. I refuse to consent to this until more information on benefits/risks is available.


  5. My 14-year-old daughter has familial hypercholesterolemia. She is on lovastatin, and her cardiologist wants to add ezetimibe. I refuse to consent to this until more information on benefits/risks is available.


  6. Dr. Aberegg above: ".. If I were a patient, I would want to be taken off this drug and be put on atorvastatin [Lipitor] or simvastatin [Zocor] or a similar agent."

    My question regarding this and cholesterol lowering by other means is: what does one want to achieve with that? There is mathematical certainty that Lipitor will never extend a life in anyone. There is certainty that cholesterol lowering will not extend the life of a women qualifying for a clinical trial so far, and Lipitor's largest study ended with 2 FEWER women having heart attacks on placebo. The still available off patent lovastitin [Mevacor; about $55/month] had mega studies in the early 1990's that both ended with more deaths on this statin.

    What really is all that 'event' benefit we are supposed to achieve? Are they trips to the hospital [yes, in some studies] or are they hard heart attacks and fever deaths [not in women, elderly, diabetics, people with peripheral artery disease and about 99% of the younger men taking a statin for a year]. Vioxx reduced the trips to the knee surgeon by reducing joint pain and Lipitor reduces chest pain, angina, and thus fewer visits to the cardiologist; we know how and why that is so.

    If one believes that cholesterol is 'evil' and the cause of disease, well these drugs and many others do work. The Vytorin, Lipitor and Crestor people probably spend $3b/year promoting cholesterol fear and they have the drugs to alleviate that fear, but do they save lives? Interestingly, good studies with Lipitor show that the calcification of the heart [valve] and arteries continues at the same speed regardless high dose Lipitor. So are we being lulled into a false sense of security while the damages continues to get worse? Well that's the evidence. Have a look at and at this picture:

    The whole benefit picture in people over age 60 is shrouded in bad science, hype and unfounded fear of cholesterol, and virtually NO benefit in deaths and of serious heart attacks. It is time doctors start telling people that their chance of living a day longer by lowered cholesterol is zero in women and close to that in men over age 60.

    Dr. Bernard, above is right: cholesterol is a 'surrogate' endpoint and in any kind of population study, those in the lowest 25% for cholesterol live the shortest.

  7. I have familial hypercholesterolemia. Most in my family do too and none of us have cardiovascular disease. We are aged 14 to 97 who have been tested and told we have FH, with the total cholesterol in the 300s to 500. We are highly active and athletic and all very healthy. The only diseases we have in fact, were caused to four of us when we took statins. An elderly family member nearly died on statins after only a short course. She now looks forward to her 100 birthday. None of us will take them and we are adamant no 14 year old in our family will ever be put on them either.

    Read about statins here, at the Statin Effects Study website of Dr. Beatrice Golomb, who is head of a $5 million NIH funded study into statin adverse effects.

  8. To anonymous who has FH: there are some people with FH who live a normal lifespan even without treatment. Currently, we don't have a good way to predict who those people will be. My husband's maternal grandfather died of a heart attack at 35, his maternal uncle died of a heart attack at 40, and his mother had a non-fatal heart attack at 58. My husband is asymptomatic, but he had a coronary artery calcium scan recently and his score was 488, which means he's at risk for having a heart attack.

    My husband and daughter are not having any side effects so far. We'll just have to see how it goes.


  9. I would say yes we do have a fairly good idea who can expect some protection from statins Marilyn. Middle aged men who've already had a heart attack. Read the article by Drs. John Abramson and James Wright in Lancet January 2007. Also read Therapeutics Initiative Letters #48 and #49. Read Medical Consumers Maryann Napoli in conversation with John Abramson, and learn why and how you've been completely snowed on this statin/cholesterol issue in
    Marcia Angell's The Truth About the Drug Companies.

    Do it for your daughter.

  10. There are thousands of people who took statins and who didn't have adverse effects, until they did. By then the damage had been done. Those people are now disabled by them and some are being diagnosed with probable statin induced ALS, Parkinson's disease (google WHO and Parkinsons AND statins), Alzheimer's, multiple strokes, irreversible peripheral neuropathy and aphasias. Statins do cross the blood/brain barrier.

    Read through the Statin Effects Study before you take a statin for prevention.

    Informed consent may be an unreachable goal in this era of drug companies witholding adverse effects information, but we must try, both to learn all we can, and to change pharma's stranglehold on our healthcare choices and delivery.

  11. I am already familiar with the sources you are citing.

    The Statin Effects Study has not come out yet.

  12. There have been several studies/articles which have come out of the Statin Effects Study. There was never going to be *A* study.

    I urge everyone using statins to read the Statin Effects Study website. You may not be having side effects, you may not be recognizing side effects or attributing them to ageing, arthritis, fibromyalgia, overwork, stress etc; either way, there is information here patient/consumers may not receive from their physicians.

    All the side effects experienced by over 1,000 questionnaire respondents and other valuable information is here.

    You're invited to fill out the questionniare about your experiences on statins; good, bad or indifferent.

  13. I assumed you were referring to the ongoing study described as follows on SES website:

    "We are currently undertaking a separate, observational study, The Statin Effects Study. We are interested in the experiences of people presently or formerly on statins, who have noticed any side effects (or benefits) while on these drugs. We are also interested in hearing from people who did not notice any change in order to to help identify characteristics that may predict risks and benefits while on statins."

    The problem with this kind of study is that there is no way of knowing whether or not the symptoms people are reporting come from statins. I don't doubt that statins have side effects. I just don't think this type of study can help us in knowing what they are and how frequently they occur. For that you need a randomized placebo-controlled trial.

    Don't forget that heart attacks and strokes cause high rates of mortality and morbidity. Each person has to weigh the risks and benefits based on their individual situation and preferences.

  14. I'm enjoying the lively debate here and I do not wish to disrupt it. However, I feel compelled, as author of the blog to state for the record that in my [highly skptical] opinion, there is little doubt that statins, in appropriately selected patients have benefits which FAR outweigh their risks.

  15. FAR outweigh? How come that there is never a mortality benefit in anyone --except for HPS and 4S and then in men only and then only starting at 1.5 years and ending about 2-3 years later?

    With Lipitor no one will ever be saved and no female heart attack ever prevented, AND calcification continues, AND, but this has never been quantified in a trial but it is real: the patient seeing his/her happy doctor's face with cholesterol 'well under control' will have that extra doughnut, fry or desert.

    A friend of mine under the 'care' of a well known doctor for 10 years on statin and 2 diabetes medications was an example of the 'everything is under control thus let's eat' picture. In the last 2 years he got bypasses and lost 2 toes to diabetes. If there is justice, his doctor himself just got a stent installed.

    So, let's look at the HARD endpoints, not the combined soft ones. The numbers needed to treat with for example plant and fish omega-3's to prevent the second heart attack are WAY smaller and since the cholesterol does not change, the person may be more motivated to change the pattern that caused arterial decline in the first place.

    To Marilyn Mann: hypercholesterolemic families in the 1850's may well have lived longest, see figure 2 here:
    Here's yours truly in a Journal:

  16. Follow-up to Marylin, I guess the high 'calcium score' of your husband confirms that statin indeed does not slow that process one iota. A daughter on statin better not get pregnant; a recent animal study I tripped over: deaths in pups and mothers. There is also good data about women accidentally on statin while pregnant and while one cannot do statistics with these data, it is scary.

    I think atherosclerosis is mainly caused [but not quickly cured] by homocysteine, a toxic amino acid ONLY lowered by high intake of 4 or 5 B-vitamins. That'd better be true ... and the reason that the 1850's people with genetically high cholesterol may have lived longer. This was before the massive food revolution that lowered the vitamin, omega-3's and magnesium intakes we currently experience.

    About LDL: I think it's what you put INSIDE this emulsion rather than the amount of the emulsion particles that counts:

    1. Within 20 minutes of eating trans/deep fry or margarine fat or fried sugar/protein products having 'AGE's', we can measure these as toxic components in the LDL droplets, and then they get into your cells.

    2. On the other hand, omega-3 fats and or carotenoids [from coloured veggies and fruits] also almost instantly wind up in the LDL and thus into your cell which is a good thing!

    3. Low B-vitamin intake in the form of a high dose multivitamin causes that blood toxin homocysteine to be high, and that ALSO travels on LDL and that ain't good. Finally oxidized cholesterol from products with egg and milk powder also winds up in the LDL: not good

    The trick is thus, we can only hope, to have your LDL be filled with healthy stuff and not with some of the harmful products that are high because how people near supermarkets eat.

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  18. Hi Dr. Scott, if there is liver toxicity with zetia then why does the Government continue to let such drug to be out in the market? If to buy zetia ( leads to a more complication than cure, what is the best alternative?

  19. I don't think that Zetia/vytorin should be on the market.


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