STOMP: Atorvastatin Doesn't Reduce Muscle Strength

Reed Miller

December 04, 2012

HARTFORD, Connecticut — Six months of high-dose atorvastatin does not sap patient's muscular strength, but it does increase creatine-kinase levels and can lead to muscular pain, results of the STOMP trial show [1].

Although physicians have frequently claimed that statins cause muscle pain, the effect of the drugs on muscle function has not been carefully observed in clinical trials prior to STOMP. The results of the trial, led by Dr Beth Parker (Hartford Hospital, CT), are published online November 26, 2012 in Circulation.

"There have emerged, over the past few years, a lot of patients [on statins] who complain of this muscle aching, and it's pretty nonspecific," senior investigator Dr Paul Thompson (Hartford Hospital, CT) told heartwire . "Doctors were seeing a fair number of patients who complained about muscle aching, and some patients complained about muscle weakness, but the literature didn't support that there actually was this problem. So we undertook this study to really focus on whether patients got weaker and what happened with their muscle complaints."

The STOMP researchers chose atorvastatin for their study because it is widely available and prescribed so frequently, Thompson said. STOMP randomized 468 subjects to 80 mg daily atorvastatin or placebo. The subjects underwent exercise testing (including a questionnaire; handgrip, elbow-flexor, and knee-extensor strength testing; and a knee-extensor endurance exercise) after six months or after they reported muscle symptoms of statin-induced myalgia.

The patients on atorvastatin showed a significant 20.8-U/L increase in creatine kinase, and 40 atorvastatin patients vs 29 placebo patients demonstrated creatine-kinase levels over the upper normal limit. The increase in creatine kinase, a biomarker of muscle damage, suggests that statins produce mild muscle injury in even asymptomatic patients.

The study confirms the "previously undocumented impression" that statins increase muscle pain, Parker et al point out. New, otherwise-unexplained muscle pains were reported by 23 of the atorvastatin patients vs 14 placebo patients, while 19 atorvastatin vs 10 placebo patients' pain was persistent enough to be classified as myalgia (p=0.05). Myalgic subjects on atorvastatin reported mostly leg symptoms, while the myalgia seen in the placebo patient was more diverse. Myalgia tended to show up sooner in the atorvastatin patients than the control patients.

However, the atorvastatin patients and control patients showed no differences in muscle strength, endurance, aerobic performance, or physical-activity levels. Physical activity decreased regardless of drug treatment, but the decrease in the atorvastatin group was driven by a drop in activity among the oldest tertile of study subjects.

"It's very reassuring that at six months of treatment, we didn't see any decrease in exercise performance," Thompson said.

Some Patients May Be at Greater Risk for Statin-Related Muscle Pain

He cautioned, however, that the study looked at only six months of statin therapy and enrolled an equal number of men and women in three age groups, 20 through 39, 40 through 54, and 55 and older. "So the next thing that needs to be done is a study like this that treats primarily older people and treats them for a longer period of time." He also suggested that a study of patients who have already reported muscle pain while taking statins could further clarify which patients are most at risk for muscle problems with statins.

Thompson also acknowledged that different statins might carry different risks of muscle damage from those of atorvastatin. He said that some researchers have suggested other statins such as rosuvastatin (Crestor, AstraZeneca) are less risky because they are primarily water soluble as opposed to fat soluble and therefore less likely to get into the muscles. Also, pitavastatin (Livalo, Kowa Pharmaceuticals America) may be safer because it doesn't change the levels of coenzyme Q10 in the muscle. But neither of those hypotheses has been rigorously tested, Thompson said.

The STOMP study was funded by the National Heart, Lung, and Blood Institute/National Institutes of Health. Thompson reports receiving research grants from the NIH, GlaxoSmithKline, Anthera, B Braun, Genomas, Roche, Aventis, Novartis, and Furiex; serving as a consultant for AstraZeneca, Furiex, Regeneron, Merck, Roche, Genomas, Abbott, Lupin, Runner's World, Genzyme, Sanofi, Pfizer, and GlaxoSmithKline; receiving speaker's honoraria from Merck, Pfizer, Abbott, AstraZeneca, GlaxoSmithKline, and Kowa; owning stock in General Electric, JA Wiley Publishing, Johnson & Johnson, Sanofi, and Abbott; and serving as a medical legal consultant on cardiac complications of exercise, statin myopathy, tobacco, ezetimibe, and nonsteroidals. The coauthors report no conflicts of interest.