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Introduction: Side Effects of Statins

Rob Orman, MD, Anne Peters, MD, and Heidi James, MD

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Are all these statins really making people healthier?

  • Two of the most common side effects and reasons for discontinuation of statin therapy are myalgias and iatrogenic diabetes.  

    • Myalgias:  Although clinical trials show a relatively low incidence of myalgias due to statin use, recent literature indicates that real world patients (including the types who would have been screened out of the clinical trials) have a much higher incidence of muscular symptoms.  

      • A 2014 review suggested no increase in myalgias for patients receiving statins versus those on placebo.  According to this report, myalgias are considered nuisance adverse reactions or random events. Joy, Tisha R., et al. "N-of-1 (single-patient) trials for statin-related myalgia." Annals of internal medicine 160.5 (2014): 301-310. PMID: 24737272

      • In contrast to the Annals of Internal Medicine findings, Heidi James finds that around 30% of her patients trialed on statins experience myalgias, and the majority of those have symptom relief when stopping therapy.

      • For high risk patients who have myalgias due to statins, James recommends that her patients first try a lower potency statin.  If they are symptomatic even after trying a second agent, she adds Coenzyme Q10 (dosed at 200 mg daily) to see if that alleviates the symptoms and makes the medication more tolerable.  Coenzyme Q10 is not well studied and potential adverse effects are unknown.

    • Iatrogenic diabetes:  In Peters’ expert opinion, statins can affect glucose uptake and cause a slight increase in glucose levels.  Patients who are on the spectrum of diabetes, such as those with pre-diabetes, may have an increase in glucose levels that tips towards diabetes.  In high risk patients, the benefits of statins, in terms of the reduction in cardiovascular events, outweighs the risks associated with a small increase in glucose levels.

      • A subgroup analysis of several studies found that women, the elderly, and Asians were at higher risk for new onset diabetes with statin therapy.  This can occur in 30% of patients.  In these studies, diabetes was defined as a blood sugar of greater than 7 mmol/L (or 126 mg/dL).  The diabetogenic effect was dose-related.  Goldstein, Mark R., and Luca Mascitelli. "Do statins cause diabetes?." Current diabetes reports 13.3 (2013): 381-390.  PMID:  23456437  

      • The long term impact of statins is unknown.  Whether statins increase the risk of other diabetes-related diseases (such as blindness, renal failure, or cardiovascular disease) has not been studied.

mike p. -

will you switch to a water soluble statin first before lowering dose or D/C in higher risk patients with myalgias?

Rob O., MD -

Hey Mike! Here is the response from David Newman....

There is no data of which I am aware that suggests that switching statins based on water solubility will change myalgia reactions. There is some data suggesting the possibility that reduction from high intensity (i.e. dose) to low intensity may reduce myalgias, and I have seen clinicians do this. Given the finding in some data that patients on statins exercise less, suggesting the possibility of subclinical myalgias, I would probably just take patients off of the drug if this occurs, as the small benefits that might occur in very high risk patients may be eclipsed in these cases. Of course, this neutralizing phenomenon (in which the benefits are negated) wouldn't be seen in trials, because virtually all trials used run-out phases that removed patients that had adverse events after a month of taking the drugs.

Short version: would probably just take a patient off of that class of drugs if clinical myalgias occur.

Heidi J., MD -

Hi Mike -

I used to try switching from one statin to another before stopping therapy, usually rosuvastatin to atorvastin and vice-versa, but unfortunately haven't had great sucess with this approach.

On a related note, I continue to be surprised at the power of suggestion regarding myalgias and statins.

When I take a patient off their statin, I ask them to come back in 4-8 wks so we can revisit the matter. Not infrequently, they report that the mylagias didn't get better off the med and they now believe if it was just their "regular aches and pains" all along. Which is likely in many cases. I've been able to restart and maintain statin therapy in some high-risk folks with this "trial of cessation" therapy. Haven't checked out the literature on this, but pretty good results in my practice.

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Red, Hot and Achy! Full episode audio for MD edition 170:22 min - 80 MB - M4AHippo Primary Care RAP February 2015 Summary 323 KB - PDF

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