SAN FRANCISCO – When patients develop myalgia on statin therapy, consider lowering the statin dose and adding ubiquinone, or switching them from a statin to red yeast rice, Dr. Douglas S. Paauw said.
Statin-related myalgias are more common in patients with low body mass and, because of metabolic variations, in patients of Asian descent.
Training emphasized the potential for liver effects and rhabdomyolysis from statins, but 20 years of evidence now shows that statins do not cause chronic liver disease, rare patients get acute liver injury, and about 0.01% of patients develop rhabdomyolysis from drug interactions with statins.
Dr. Douglas S. Paauw
Muscle pain is the most common statin side effect, he said. Studies suggest that 5%-18% of patients on the highest doses of statins will develop myalgia.
In one recent prospective, blinded study, 420 healthy, statin-naïve participants were randomized to 80 mg of atorvastatin or placebo for 6 months. Significantly more statin users (19) developed myalgia than did those on placebo (10). Creatine kinase levels increased significantly by an average of 21 U/L in atorvastatin users, suggesting that, even without symptoms, statins cause mild muscle injury (Circulation 2013;127:96-103).
Statin package inserts suggest that 1%-2% of patients will develop myalgia; however, early studies of statins did not look for myalgia, and the real-world rates of statin-related myalgia may be as high as 20%-30%, Dr. Paauw said at the annual meeting of the American College of Physicians.
The trick to avoiding this side effect is titrating the dose upward until you achieve lipid control. "Cardiologists often want to start people at high doses, and they have reasons for that. In general medicine, I certainly am a believer in getting patients started on a reasonable dose and then pushing up the dose. Once they get myalgias, patients are often reluctant to trust taking more statins. I like to prevent myalgias from happening in the first place," said Dr. Paauw, professor of medicine at the University of Washington, Seattle.
When a patient on a statin complains of muscle pain, check the creatine kinase level to see how big the problem is, and check the patient’s thyroid-stimulating hormone (TSH) level. Severe hypothyroidism can raise lipid levels and cause myalgia that looks just like statin-related myalgia. "When you treat the hypothyroidism, you may have much more success with a statin," he said.
The next step is to stop the statin to see if the myalgia goes away. "Patients should get better in a few weeks if it’s statin-related myalgia," he said. If symptoms disappear, restart the statin at a lower dose or switch to a different statin. One study found that myalgia rates on the highest dose of each respective drug ranged from a low of 5% with extended-release fluvastatin to 11% with pravastatin, 15% with atorvastatin, and 18% with simvastatin (Cardiovasc. Drugs Ther. 2005;19:403-14).
If myalgia recurs after switching, try switching again. Consider specific low dosages: extended-release fluvastatin 80 mg daily or every other day, or twice-weekly atorvastatin 10 mg, or low-dose rosuvastatin daily every other day or weekly, Dr. Paauw said.
But don’t completely sacrifice lipid control for side-effect management, he added. "The problem is that fluvastatin is about equal to giving jelly beans" for lipid control. "My view is that a little statin is probably better than no statin. Many of these patients have gotten to the point where we can’t use anything" at normal statin dosages, he said.
When switching statins doesn’t make a difference, it may simply mean that some patients are going to get myalgias with statins or they won’t, he added.
Discuss with the patient whether they want to consider adding ubiquinone (coenzyme Q10) to statin therapy. One positive study suggesting that coenzyme Q10 may reduce statin-related myalgia has been followed by several negative studies. One recent study randomized 76 statin users who developed myalgia in two or more extremities to statin treatment with twice-daily placebo or coenzyme Q10 at 60 mg. Visual analog pain scores did not differ significantly between groups after 1 month (Am. J. Cardiol. 2012;110:526-9).
"I think it’s still okay to try [coenzyme Q10]. It’s benign, and you may get a placebo effect," and there’s some scientific basis for why it might work, he said. Patients on statins have low ubiquinone levels, and coenzyme Q adds it back. "I think the jury is still out in this."
Another reasonable option to consider is to switch from a statin to red yeast rice, whose active ingredient is 4-5 mg of lovastatin, he said. One study randomized 62 patients who stopped statins due to myalgias to 24 weeks of twice-daily placebo or 1,800 mg of red yeast rice. The red yeast rice group had a significantly greater decrease in LDL cholesterol levels (35 mg/dL) than did the placebo group (15 mg/dL). Pain severity scores did not differ significantly between the two groups (Ann. Intern. Med. 2009;150:830-39).