Statins and Muscle pain

Reuters Health Information CME

Benefits of Statins Outweigh Musculoskeletal Effects, Say ExpertsCME

Clinical Context

Statins are usually well tolerated, but the most common adverse effects are musculoskeletal, including muscle aches and pain, weakness, cramps, or increases in creatine kinase levels. In the general population, little is known about the prevalence of musculoskeletal pain and statin use.

Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 had suggested an association between statin use and musculoskeletal pain among individuals without arthritis, but the relatively small sample size precluded determination of whether statins increased musculoskeletal pain in those with arthritis.

The objective of this study by Buettner and colleagues was to evaluate the association between statin use and musculoskeletal pain in the general population, including those with and without arthritis, using 6 years of NHANES data.

Study Synopsis and Perspective

In a cohort of people without arthritis, musculoskeletal pain, most often in the legs and lower back, was reported 33% more often by those using statins.

"Although the majority of people who use statins do not experience statin-associated musculoskeletal side effects, about 6% (or one out of every 17 people) without arthritis have pain associated with statin use," Dr. Catherine Buettner, who led the study, told Reuters Health.

In people who do have arthritis, statins didn't seem to add to the pain burden — although the pain of arthritis could mask statin-associated pain, she and her colleagues say.

Dr. Buettner, from Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, added, "Our study did not allow us to discern why those with arthritis do not report higher pain when using statins. Statins are known to have some anti-inflammatory effects so, theoretically, it is possible statins may decrease arthritis pain by decreasing inflammatory processes."

"On the other hand," she said, "most arthritis is due to osteoarthritis (rather than inflammatory arthritis), so we need to consider other reasons; it could simply be that pain from arthritis is more severe and masks mild-moderate pain related to statin use; it may be that patients with arthritis are more reluctant to start a statin, or discontinue them more frequently, due to concerns that using a statin is adding to their pain; or it may be that doctors are less likely to prescribe a statin to patients with painful musculoskeletal conditions, such as arthritis."

Statin drugs are one of the most widely prescribed classes of medications. In 2003-2004, an estimated 24 million adults in the United States received a prescription for one. Although generally well tolerated, musculoskeletal side effects, including muscle aches, pain, weakness, cramps or creatine kinase elevations are the most common adverse effects of statins.

Asked for his thoughts on the new findings, Dr. Harlan Krumholz of Yale School of Medicine in New Haven, Connecticut, who was not involved in the study, said: "It's an observational study and has some limitations. Nevertheless, we know that statins can cause some muscular discomfort — and this article is consistent with that knowledge."

"The bottom line," he told Reuters Health, is that the "33% relative increase in risk translates to a few additional patients feeling discomfort for every 100 treated. This study should not deter patients from taking their medication — or shake their faith in the powerful risk reduction effect of statins — but people with these complaints should talk with their doctors."

Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, Dr. Buettner and colleagues estimated the prevalence of self- reported musculoskeletal pain according to statin use.

The analysis, reported in the February issue of the American Journal of Medicine, included 8,228 adults (representing 113 million US adults) aged 40 and older; 1,306 of them (representing 17 million US adults) reported using a statin in the past month.

Statin use increased significantly over the study period, with prevalence of use in the last 30 days estimated at 13% in 1999-2000, 15% in 2001-2002, and 18% in 2003-2004.

Musculoskeletal pain was assessed by asking participants: During the past month, have you had a problem with pain that lasted more than 24 hours? Those who answered "yes" were asked where the pain was.

In the overall sample, the unadjusted prevalence of musculoskeletal pain was significantly higher among statin users reporting pain in any area than nonusers (30% vs 26%; p=0.007); in the lower extremities (18% vs 14%; p=0.008); and in the lower back (14% vs 11%; p=0.02).

After controlling for confounding factors, among the 5,170 subjects without arthritis (about 63% of the complete cohort), statin use was associated with a significantly higher prevalence of musculoskeletal pain in any region, the lower back and the lower extremities. The adjusted prevalence ratios were 1.33, 1.47 and 1.59, respectively.

Conversely, there was no association between musculoskeletal pain and statin use among the 3,058 adults with arthritis.

"Being aware that statins may cause musculoskeletal pain is important and should be considered when new symptoms start in a patient who has recently started a statin, had an increase in statin dose, or started a medication that interacts with a statin," Dr. Buettner said.

"However, it is also important to recognize that the background prevalence of musculoskeletal pain is high among adults (more than 20% in non-statin users in this study). Therefore the majority of people using statins who have muscle symptoms are more likely to have symptoms due to another cause rather than due to use of a statin," she commented.

Dr. Krumholz agrees. "Many people have musculoskeletal pain, and for those on a statin the pain could be unrelated." However, the use of statins "is associated with an increased risk of muscle discomfort and that adverse side effect can be evaluated by discontinuing the statin and seeing if it goes away."

It should also be recognized, he said, that the musculoskeletal side effect "is not consistent across statins and people should try another one if they do have this side effect, in collaboration with their doctor."

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Am J Med. 2012;125:176-182.