Cholesterol-modifying drug that does more harm than good is withdrawn from sale

Niacin is a form of vitamin B3 that has been long-known to reduce levels of ‘unhealthy’ LDL-cholesterol, while raising levels of ‘healthy’ HDL-cholesterol. It’s generally believed that these effects would translate into better outcomes in terms of cardiovascular issues such as heart attacks and strokes. As a result, niacin has a history of use for modifying cholesterol levels, particularly in those deemed to be at relatively high risk of cardiovascular problems.

However, the truly important thing is not the impact any drug or intervention has on cholesterol levels, but the impact it has on health. We could find that arsenic is fantastic at reducing LDL-cholesterol and raising HDL-cholesterol, but that wouldn’t make it an automatic good choice for our health, right?

Anyway, on the basis of its cholesterol-‘improving’ effects, niacin became an established therapy. And in 2008 the European Medicines Agency gave the green light to combination drug known as Tredaptive. This product contained niacin combined with another agent known as laropiprant, which had the ability to reduce the propensity for niacin to cause flushing (a common side effect of niacin that is generally experienced as heat and redness in the face and/or body).

Tredaptive was available in dozens of countries, but in January of this year its manufacturers (Merck) announced that it was being withdrawn. This week saw the presentation of the results of a study on Tredaptive that explains the withdrawal.

The study involved more than 25,000 people who had a previous history of cardiovascular disease (such as a previous heart attack or stroke). All the individuals in the study were on cholesterol-reducing medication (the statin simvastatin with or without the drug ezetimibe). Individuals were randomised to get Tredaptive or placebo (dummy pill). The average length of treatment was about 5 years.

The addition of Tredaptive was found to bring no benefits at all in terms of risk of heart attack, stroke or overall risk of death.

However, those taking Tredaptive were at increased risk of certain side effects including:

  • bleeding
  • infection
  • diabetes
  • diabetic complications in those with diabetes
  • muscle damage (myopathy)
  • gastrointestinal symptoms
  • rashes

In summary, Tredaptive clearly did significantly more harm than good.

Here’s a video of one of the study’s chief investigators, Professor Jane Armitage from the University of Oxford, talking about this study and its findings.

The results of this study are yet another reminder of the inescapable fact that we cannot judge the value of a drug based on its impact on cholesterol – we need to know the effect it has on health. All too often, we find that the supposed benefits of a drug do not materialise in reality. And sometimes, we find the results are actually far worse than doing nothing.

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20 Responses to Cholesterol-modifying drug that does more harm than good is withdrawn from sale

  1. SmartEaters 14 March 2013 at 4:24 pm #

    Interesting.

    A few comments:

    Is it correct to suggest (as arguably your opening sentences above could be said to so) that niacin has been found suspect as a result of this study?

    1) This study didn’t test niacin! It tested niacin plus Laropiprant together, branded as Tredaptive.

    2) There was no control! Worse again, all participants were multiply medicated with additional dosing with statins and with ezetimibe (about which there have been safety concerns)

    Dr Briffa, do you have a view as to whether niacin itself is perfectly safe? What about other so-called “no-flush” options? For example, inositol hexanicotinate?

    Wouldn’t it be a real shame if a wrong interpretation of what this study has “proven” (nothing it seems!) would rob us all of what has always appeared to be one of the very safest and cheapest of the “cholesterol controlling” options out there? Tipping more folk into the statins trap?

    Your point about the ridiculous obsession about cholesterol is well made and one I share but that’s a different matter really.

    Thanks

    Conor at SmarEaters.org

  2. Rakesh Patel MD 14 March 2013 at 4:55 pm #

    Context is everything. The baseline numbers in this study were: TC 128 LDL-C 63 HDL-C 44 TG 125 mg/dL. No one in there right mind would add anything to this patient population. Not to mention no niacin only group studied

  3. Kerry 14 March 2013 at 5:03 pm #

    Is Niaspan beneficial, or should it be discontinued, also?

  4. R. Ludlow 14 March 2013 at 5:09 pm #

    Very interesting but surely this does not reflect negatively on the use of immediate-release niacin to normalize blood lipids?

    I’ve read that slow- or delayed-release niacin can be hepatotoxic in larger doses but that immediate release niacin, if you can stand the flush (I like it), is still OK. I take 750mg in the morning wth magnesium and repeat before bedtime. Dr. Abram Hoffer worked with niacin therapies for decades, along with other orthomolecular work with Dr. Linus Pauling (of ascorbic acid/Vit. C fame). They both lived into their early 90s.

    Other than the flush, which some find unpleasant if unexpected, and the risk of liver damage at higher sustained doses, don’t the benefits of niacin use outweigh the risks?

  5. Angela 14 March 2013 at 7:31 pm #

    Ironic given that it is perfectly possible to take niacin in a form that does not cause flushing, but perhaps this doesn’t have cholesterol-lowering effects?

  6. iRememberWhen 15 March 2013 at 5:27 am #

    So is the moral of this story then that we need to flush when we take niacin for it to be effective? The niacin helps our mitochondria uncouple electrons and release the excess energy as heat instead of keeping it bunched up to aggravate inflammation? If we suppress the flushing, we suppress the heat-dispersing, anti-inflammatory function of niacin and so lose all the benefits?

  7. Dick 15 March 2013 at 7:06 am #

    Considering the longer list of side effects that the popular cholesterol lowering drug class, statins produce, are we going to see that withdrawn from sale?

  8. Dr John Briffa 15 March 2013 at 10:31 am #

    Re niacin:

    This study did not test the effects of niacin (but a combination of niacin and laroprprant), and it’s findings cannot be extended to niacin (alone).

    A recent review of the evidence suggests that niacin has the ability to reduce cardiovascular events (e.g. heart attacks). See here: http://www.ncbi.nlm.nih.gov/pubmed/23265337

  9. Dr. Neville Wilson 15 March 2013 at 11:38 am #

    I believe that there is enough supportive evidence for the safety and efficacy of Niacin. The problems arise with pharmacological concoctions that are profit driven rather than health supportive initiatives.
    Any one of several combinations of the concoctions used in this trial could have been a cause for the outcome.

    See my article on “The Rise and Fall of Tredaptive ” in The Irish Medical Times, or http://www.drnevillewilson.com

  10. SmartEaters 15 March 2013 at 1:05 pm #

    Great! Thanks for that. Indeed the impact of anything on cholesterol levels isn’t my concern: my interest was in the general safety of niacin as a supplement. ( I have worked with a few people using large doses for mental health reasons and would be concerned if there were a trade off to consider). The recent study you link to is interesting in that firstly it’s a meta-study; next, it suggests that niacin typically seems to confer CVD risk benefits and finally it cites the possibility that indeed the mechanism may be other than via change in HDL levels.

    The from of niacin I prefer is inositol hexanicotinate: mixed studies on impact on
    cholesterol profiles but most importantly, apparently safe. See here for summary:

    http://www.efsa.europa.eu/en/scdocs/doc/ans_ej949_Inositol_hexanicotinate_op_en_REV.pdf

  11. Janet 15 March 2013 at 2:31 pm #

    The one thing we’ve not emphasised so far is that this trial was carried out on people who were already on a statin drug (if I’ve understood it right), and the niacin preparation was added (or not) to the regime. Maybe the adverse outcome was due to an interaction between the two? Or the combination drove cholesterol levels down too far? (Which is as bad as having high cholesterol)

  12. Maura 15 March 2013 at 3:10 pm #

    My husband was one of the participants of this study. He did not have a heart attack or stroke. His family had a poor heart history. He did not have raised cholesterol levels. He suffered a substantial stomach bleed and was admitted to accident & emergency and had several packs of blood administered. His memory was badly impaired and his doctor believed he was depressed. He was sent into a treatment centre and after two months it was decided he needed further tests as it was not depression At that time I asked his Heart Consultant for a letter to stop taking the medication as I had read a lot about statins and memory loss He was moved to a psychiatric hospital and diagnosed with Fronta temp lobe Dementia and given a life expectancy
    of five years. We have commenced year three now, my dear husband is bed bound now having fractured his acetabulum and had the ball if the femur shoot through the housing because it was not diagnosed on the X-ray by the doctor on duty in A&E and was told to use the walker immediately and was given lessons in the hospital before we left. Basically I believe ‘medicine’ and it’s purveyors have stolen my husband and all too soon I will be without him. I received a letter from the Consultant last month to say the trial was at an end. He made no enquiries as to the health if my husband Other than to state he would speak on his next appointment.
    My husband will not be recorded as part if any trial. No follow up.

  13. Murray 15 March 2013 at 8:16 pm #

    In addition to Niaspan there is a non-prescription (US) time-release niacin called Endur-Acin made by endurance products in Oregon. It uses a natural substance to handle the release the niacin. I have been taking it for about 20 years and it seldom causes a flush. (Maybe once a month or so.) Also, costs less than Niaspan, which I found was not easy to take.

  14. Ian Day 15 March 2013 at 10:22 pm #

    I am T2 diabetic with total cholesterol of 5-6.

    I could not tolerate simvastatin because of muscle pain.

    A few months later Dr started me on niacin – going from 500 mg to 1,000 in 3 weeks. I was monitoring my blood glucose on rising each morning. It went up from around 6.5 to over 7 in that time, & muscle pain began again. Dr checked confirmed that increase in BG was a side effect & has abandoned any attempt to give cholesterol drugs.

    I do use cholesterol reducing margarine & this is effective at reducing chol without any side effects.

  15. Vanessa 15 March 2013 at 10:26 pm #

    Maura – thank you for sharing your husband’s experience. It is shameful that these trials take place with no consideration for the harm done to many of the participants. All they usually are interested in is a positive outcome – it’s unbelievable that this drug could have been out there, freely prescribed, since 2008!

    The goal at present seems to be to lower cholesterol at any cost – but without any regard to how this is goal is reached. Surely it’s better to achieve this aim by looking at whatever it is that causes the associated rise in cholesterol in the first place (eg raised homocysteine levels, inflammation and damage to arteries caused by insulin caused by high blood sugar caused by diet and so on) – rather than to stop the production of cholesterol at source. We have the ability to manufacture it for good reason…….is anyone having a look at how niacin might act? Tail wagging the dog, it seems.

  16. Dr John Briffa 15 March 2013 at 10:35 pm #

    Ian – what evidence do you think there is that cholesterol-reducing margarine has benefits for health over eating butter?

  17. Hilda Glickman 16 March 2013 at 12:32 am #

    Niacin is a B vitamin and B vitamins work I synergy with each other so should not be used alone. In fact as a nutritionist I would not step out any nutrient without giving a multivitamin/ mineral first.

  18. Lorna 17 March 2013 at 9:55 am #

    The underlying assumption here is that ‘high’ cholesterol levels are bad in a undiscriminating way. There are numerous posts on this blog and on many other websites and blogs that question this blanket response. Living as well as one can with a range of unprocessed foods and exercising seems to me to be better than taking medication and supplements that are not necessarily going to improve basic health. And, the experience of the triallist above is so saddening it serves as a ‘stop-and-think’ to us all.

  19. Ian Day 20 March 2013 at 6:22 pm #

    Quote: “Ian – what evidence do you think there is that cholesterol-reducing margarine has benefits for health over eating butter?”

    I eat much more butter than c-r marge, but I/we have been brain-washed into believing that reducing chol is beneficial to health. The local heart consultants are very keen of chol reduction – they deal with the results?? of high chol, though as far as I know they haven’t related known patients with high chol to subsequent heart disease.

    It’s a reasonable precaution – I can do personal research on:
    diet & blood sugar;
    diet & weight control;
    diet & stamina;
    diet & cholesterol;

    But NOT diet & heart disease, except that routine screening tests for heart health have not indicated any problems.

  20. Ian Day 20 March 2013 at 6:36 pm #

    I suggest that a possible indicator of heart health is pulse rate & recovery with exercise.

    I’m 74 with a BMI of 26 & my general health is good, with no chronic conditions apart from T2 diabetes.

    My resting PR is about 65;
    moderate exercise 90;
    vigorous exercise
    – table tennis – up to 120
    – tennis – normally about 120,
    – but after intense rallies up to 150, dropping back quickly to 120.
    After exercise, about 90 & dropping to normal.

    I feel NO ill-effects from that effort, nor do I take any energy drinks; my low carb diet with increased fats provides all the energy I need.

    What other PERSONALLY OBSERVED EVIDENCE should I look for assess the effectiveness of my diet ?

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