The safety of treatment with statins (whether you have prostate cancer or not)

In a commentary a couple of days ago we noted some diversity among medical opinion leaders about the safety of treatment with statins. Specifically, we wrote,

taking statins does come with some degree of risk for side effects that can include things like muscle aches, diabetes, fatigue, weakness, and effects on memory. However, there seems to be a considerable diversity of opinion among experts about just how common and serious such side effects really are.

In that context, in today’s issue of The Lancet, there is a highly detailed review, by Collins et al., of the of the utility and safety of treatment with statins in the prevention of heart attacks and strokes. Collins et al. deal very specifically with data related to the risks for all of the above-mentioned and reported side effects of statin therapy.

A key point, which Collins et al. go to great lengths to document, is that many of the reports about the side effects associated with statin therapy are based on less than compelling data and case series. They write that:

statin therapy may cause symptomatic adverse events (e.g., muscle pain or weakness) in up to about 50–100 patients (i.e., 0.5–1.0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (i.e., they represent misattribution).

They also note that because media reports about side effects of statin therapy are commonly based on data from case series, these reports are almost invariably about associations between use of statins and cannot be assumed to have a cause and effect relationship. In other words, just because someone is taking a statin and they subsequently start to have muscle pain or weakness does not necessarily imply that the muscle pain and weakness is cause by taking a statin at all.

Undoubtedly there are those who will dispute the findings in this long and detailed paper by Collins et al. Basically what Collins et al. are saying is that belief that as many as 20 percent of appropriately statin-eligible patients have significant side effects to statin therapy is grossly inaccurate, and that there is no good evidence to support such beliefs at all. They also point out that by not taking statins, such patients are exposing themselves to a massive increase in risk for death from cardiovascular disorders. However, as we know from observing people’s abilities to “believe” or “not believe” in global warming, data often have little or nothing to do with people’s ability or willingness to understand the risks that they are taking as individuals or as a society.

Now what is still quite certainly true is that we do not know the magnitude of the effect of statin therapy on the overall survival of men diagnosed with prostate cancer (if there is such an effect at all). We believe that there may be such an effect but we have no data from a large, randomized, placebo-controlled, double-blind trial that proves this. In the prior article, our point was solely that so many men in America of 50+ years of age should probably be on statin therapy anyway (by comparison with the number of men who get diagnosed with prostate cancer) that the effect of adding a statin to one’s treatment regimen in order to defer or avoid prostate cancer-specific mortality may be trivial by comparison with the role of a statin in prevention of risk from cardiovascular-specific mortality. This would leave us with a relatively small number of men in America who really don’t need to take a statin for cardiovascular reasons but who would still like to know whether taking a statin would have a meaningful impact on their risk of prostate cancer-specific mortality.

Life is complicated … and sometimes knowing exactly what to do to optimize the length of one’s life is complicated too.

2 Responses

  1. Wow Mike, you weren’t kidding when you described this paper as “highly detailed” – phew, 28 pages! I’m hoping to find time to study it.

    I’ve talked about my wife’s experience before, but I’ll add a little detail as it appears that one of the paper’s key claims to a low side effect burden relates to “misattribution” of adverse events, such as muscle pain, to statins when the real cause lies elsewhere.

    My wife took at least three statins simvastatin, Crestor, and lovastatin, with varied dosing and schedules in a search with her doctor to find one that was not associated with very uncomfortable pain. Her doctor, my wife and me all initially thought the pain she was complaining about was caused by her severe arthritis or might relate to hypertension or bone density medication. Gradually we homed in on statins as the likely cause. She was initially on simvastatin, and, though benefiting with a much lower cholesterol, experienced pain that seemed to be linked to the drug. She complained of a sharp pains that popped up in different areas like lightning strikes in a thunder storm. The pain gradually subsided as she took a vacation from the drugs, but it took her months to get to baseline, as predicted by her rheumatologist. (It is interesting that that doctor seemed quite familiar with muscle pain from statins.) We are convinced of the statin-pain connection because the acute pain attacks were so closely linked to her statin doses. She is now doing fine on Zetia: cholesterol benefit, but no clear link to pain.

    The paper mentions the trials that showed a very low incidence of significant pain from statins – around 1%, at least in one trial. I’ll be interested to read this very detailed discussion.

    Thanks for providing the link.

  2. Jim:

    I think we need to distinguish very clearly between your wife’s situation (which may very well be a real side effect of statin therapy; as the authors carefully observe, this does happen) and the point that they are making, which relates to the general perception that all statins have a high level of side effects, and which is based on a failure to understand the difference between “association” and actual “cause and effect”.

    The authors are not in any way suggesting that statins don’t have side effects. All drugs have side effects. What they are pointing out is that there is absolutely no Level 1 evidence of a high level of side effects of statins in any of the many large, prospective, randomized clinical trials of statins conducted to date using statins currently on the market. And some of those trials have been very specifically conducted to explore these issues.

    There were a couple of statins developed (and one that made it to market) in which the levels of side effects were higher. But the one that made it to market (in Europe) was fairly rapidly removed from the market again.

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