Rockefeller University Hospital opens clinical trial into statin-associated muscle complaints

The most widely prescribed class of drugs in the country, statins have helped millions of people lower their cholesterol and reduce their risk of heart attacks - but their side effects, including muscle pain and cramping, have proven to be something of a sore point for many patients.

Now, researchers at The Rockefeller University Hospital aim to determine the cause of statin-associated myopathy in a new clinical study. Patricia Maningat, instructor in clinical investigation in Rockefeller's Laboratory of Biochemical Genetics and Metabolism, is the study's principal investigator.

Approximately 38 million people in the United States are on statins, and medical professionals expect the number to continue rising. About 10 percent of patients taking statins report some level of myopathic symptoms, but the only marker known to gauge them - elevated blood levels of an enzyme known as creatine kinase - often shows up normal, creating diagnostic confusion and leaving many muscle complaints undiagnosed.

"We still don't know why some patients develop these side effects while others tolerate statins without any symptoms," says Maningat, whose study will test the hypothesis that statin-associated myopathy is the result of dysfunctional fuel metabolism in the muscle. Recent studies suggest that statins may inhibit fatty acid utilization, a situation that can lead, Maningat says, to muscle accumulation of fat and increased utilization of carbohydrates, potentially leading to muscle deterioration.

One hundred study participants - men 40 to 60 years old and postmenopausal women 50 to 60 years old who are taking atorvastatin (i.e., Lipitor) or simvastatin (e.g., Zocor) for less than one year, have experienced muscle symptoms and have a low risk of heart attack - will be divided into two groups. The first 20 subjects will give laboratory samples and complete two questionnaires about muscle symptoms and quality of life both before and after an eight-week course of either continuing their statin prescription or being placed on placebo.

Of the subsequent 80 subjects, 20 will be chosen to undergo four days of metabolic testing, both before and after treatment or placebo, to determine fuel use in the muscles during rest and exercise. The researchers will use magnetic resonance spectroscopy to measure the fat in muscle cells. "A higher level of fat is an indicator of faulty fatty acid utilization," says Maningat. Because the body uses more fatty acid during exercise, a calorimeter will also be used, to determine the amounts of carbohydrates, proteins and fatty acids being used during the exercise portion of the test. Subjects will also be tested on a leg press to test muscle strength, and, because new studies suggest that statins may increase the risk of diabetes, researchers will also gauge insulin sensitivity. Sixty of the second group of subjects will be recruited for the blood test and questionnaire only.

"If this study demonstrates that dysfunctional metabolism is the missing link between statins and myopathy, we'll be one step closer to figuring out why some people have these symptoms and some do not," says Maningat. "We also hope this information will help doctors diagnose statin-associated myopathy more accurately and lead to better strategies to help those so afflicted."

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