Is simvastatin the next Baycol?

As the connection between elevated cholesterol and heart disease became clear, researchers looked for ways to lower cholesterol levels in humans.  A set of compounds known as HMG-CoA reductase inhibitors (“statins”) were found to lower cholesterol quite effectively, although some early drugs (i.e. cerivastatin/Baycol) were found to have some disturbing side effects.  Especially when combined with other cholesterol medicines, cerivastatin had a high incidence of  serious muscle damage, much higher than other statins (along with allegations that unfavorable safety data may have been buried by Bayer).  Other cholesterol medications can also cause muscle damage but none to the extent of cerivastatin.  Still, in prescribing statins, physicians monitor patients for signs and symptoms of muscle damage.

Physicians were initially reluctant to prescribe statins, and drug companies such as Merck were quite anxious to sell them.  A lingering problem was lack of data showing that statins could prevent heart attacks and death.  The data showed that higher cholesterol levels put people at higher risk, but before 1994 there weren’t good data showing a direct benefit of statins.

In 1994 The Lancet published the Scandinavian Simvastatin Survival Study (usually called “4S”).  It was sponsored by Merck, the maker of simvastatin (Zocor), and is considered one of the best and most important statin studies.  Four thousand four hundred forty four patients with heart disease, high cholesterol, and being treated with a cholesterol-lowering diet were randomized to receive either simvastatin or placebo.  The results were dramatic.  They showed significantly reduced deaths in the simvastatin group, and decreased need for invasive heart procedures.  There were few safety problems.

Later studies confirmed many of the findings of 4S, and statins have become an important tool in preventing heart attacks in people with heart disease.   Other benefits have been found as well, and statins seem to have beneficial vascular effects beyond simply lowering cholesterol, but measured levels of cholesterol are still the most commonly used marker to judge the effectiveness of statins.

With all statins, a higher dose produces lower cholesterol levels, an effect that tends to taper off at higher levels (for example increasing simvastatin from 40 mg to 80 mg gives an additional drop in LDL cholesterol of about 6%).  The risk of unwanted effects such as muscle damage may also increase with higher doses, so doctors try to balance the need for lowering cholesterol with the risk of side effects.   Some of the newer statins such as rosuvastatin (Crestor) have increased potency at lower doses and appear to have a lower incidence of side effects at effective doses, but rosuvastatin is a very expensive medication.  Most other statins are available as generics for about 4-10 USD monthly.  Insurance companies have made a very strong push to encourage the use of generics, so doctors and patients are often forced to decide between paying more money, or pushing up the dose—and perhaps the side effects—of older drugs.

Today the FDA announced restrictions (consumer version) on the use of very high dose simvastatin (80 mg). Especially in combination with certain medications and in some patients, the high dose can lead to a higher risk of muscle damage.  They specifically recommended that this dose should be avoided, unless a patient has been taking it for at least a year without problems (the risk is highest during the first year of treatment).  If cholesterol cannot be controlled at lower doses, they recommend changing drugs.

This is going to cause (has already, actually) an avalanche of calls to doctors’ offices.  This risk to any individual isn’t terribly high, and most patients shouldn’t abruptly stop their medications, but people taking 80 mg of simvastatin should ask their doctor whether it is best to keep going or to make a change.

The take home message is that statins are inexpensive, safe, and effective for the prevention of heart attacks and other serious illnesses in many groups of patients, and that it often takes years to sort out the safest approach to therapy.  If you are on a lower dose of simvastatin you should not increase it to 80 mg.  If you have taken 80 mg of simvastatin safely for over a year to control your cholesterol effectively, there is no need to abruptly stop it.  For any patient concerned about their therapy, there are many safe and effective alternatives.

(Full disclosure: I’ve been taking simvastatin safely for years and have no plans to change any time soon.)


  1. A. Marina Fournier

     /  June 9, 2011

    I am so looking forward to Lipitor’s patent ending, so as to get affordable atorvastatin HCL! Now if Actos and Abilify would only fall off patent restriction, I would have less medical expense that could be used on food or car repair.

  2. bsci

     /  June 10, 2011

    The area of statin research that concerns me is the life-long taking of statins starting at young ages. Statins are recommended to people with high cholesterol as the only symptom, particularly if there’s family history of heart disease. Almost all major studies are in people with existing heart disease. Most others are in people who are significantly older. The pediatric studies I’ve seen focus solely on acute side effects and ability to lower cholesterol.

    Assuming high cholesterol alone isn’t a symptom, what does it mean to put an asymptomatic 18-year-old or younger on a statin for life? These drugs have been around long enough that it should be possible to have tracked some kids into the early ages for measurable heart disease. This is far from my own expertise, but in some cursory searches, I haven’t found any outcomes research on this population either in terms of reduced heart disease risk or adverse side effects.

  3. BB

     /  June 10, 2011

    My late mother reported myopathy symptoms to her PCP years ago- and was written off as a crank. Mother stopped taking her cholesterol-lowering med (forgot which it was) because she couldn’t stand the pain and weakness.

  4. mml

     /  June 10, 2011

    You are obviously unaware of the pharmacogenetic studies linking SNPs in a gene, SLCO1B1, which encodes a transport protein responsible for movement of statins into the liver for Phase II detoxification. Studies have noted a greatly increased incidence of severe myalgias and myopathies in individuals with either of 2 identified mutations, necessitating discontinuance of the statin. In addition, plasma statin levels were measured in study participants with these SNPs; one major study noted AUCs of 400% above normal for those taking a statin with one of the identified SNPs. I think for the unlucky ones who do not develop myalgias or myopathies necessitating discontinuance of the drug, neurodegenerative diseases develop.
    These are NOT rare mutations. Perhaps reading the dissertation from the following web link would assist you in further understanding the true potential dire effects of statin use:

    • PalMD

       /  June 10, 2011

      When a comment starts with “You are obviously unaware of…” everything that follows is pretty much assumed to be annoying, useless crap. It could be the latest Nobel-winning hunk of knowledge, but I’ll never know, because I never read past that.

  1. Death knell for simvastatin | White Coat Underground
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