Do statins (a class of cholesterol lowering medication) really cause muscle pain? This discussion has been going on for decades. The Mayo Clinic even has a statin intolerance clinic run by San Antonio native, Dr. Steven Kopecky. The longstanding statistic is that 10% of patients who take them experience muscle pain, but that so do 10% of patients who take placebo. Here is the latest study on the topic from the British Medical Journal, the BMJ. The first is an article on the study from The New York Times followed by the abstract and a link to the original article.
Do Statins Really Cause Muscle Aches?
Many people who take the cholesterol-lowering statin drugs report that they cause muscle pain, but a randomized trial suggests that the pain is no different when they take a placebo pill.
In rare cases, statins are known to cause a severe muscle condition called rhabdomyolysis, in which skeletal muscle tissue is destroyed, leading to serious complications. But much more frequently, people complain that the drugs simply cause muscle pain.
Whether statins are responsible for the muscle pain, however, remains uncertain. Muscle pain has many causes and is common in the older age group using statins, so determining whether statins are causing the pain is not easy. Results from observational studies, along with many media reports, may have led some to unnecessarily discontinue a treatment that is potentially lifesaving.
This new study, published in BMJ, involved a series of what is known as n-of-1 clinical trials, a methodology that allows researchers to examine the results of treatment and placebo in individual patients, rather than studying them as a group. In effect, each patient serves as his or her own control.
Researchers assembled 200 people in England and Wales who had either stopped or planned to stop taking statins because of intolerable muscle pain. For a year, each patient randomly took either a statin or a placebo pill over six two-month periods. Half the time they received 20 milligrams of Lipitor, and the other half they got a look-alike dummy pill. Until the end of the study, neither the researchers nor the patients knew when they were taking the statin and when they were taking the placebo.
During the last seven days of each two-month phase, the researchers measured each patient’s pain daily using a validated 10-point visual pain scale, with 10 indicating the worst possible pain. They also tracked other aspects of daily life, including the patient’s general activity level, mood, comfort in walking, ability to pursue normal work activities, social relationships, sleep and enjoyment of life.
The study found no differences between the statin and placebo periods in either muscle pain or reports on daily life activities and moods. Nine percent withdrew because of pain while they were on statins, but so did 7 percent who were taking placebos, an insignificant difference.
“These studies are difficult to do,” said Dr. Henry N. Ginsberg, a professor of medicine at Columbia who was not involved in the work. “This one is done as well as you can, and it’s a nice one to talk about with patients. You can tell your patients, ‘They’ve done studies in people like you, and these people couldn’t tell the difference between placebo and medicine.’”
Three months after the final treatment, when the patients had been informed of their results, the researchers asked them whether they had restarted statins, or intended to, and whether they found their own trial result helpful in making their decision. Most of the patients said that the trial was helpful, and more than two-thirds reported that they planned to start taking statins again.
The lead author, Dr. Liam Smeeth, a primary care physician and professor of clinical epidemiology at the London School of Hygiene and Tropical Medicine, said that when people stop statins because of muscle pain “they’re missing out on the huge benefits — reducing the risk of heart attack or stroke by about a third. What we’ve shown is that among these people who gave up their medicine because of pain — and their pain was real — it wasn’t made worse by statins.”
Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials
BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n135 (Published 24 February 2021)Cite this as: BMJ 2021;372:n135
- Emily Herrett, assistant professor1,
- Elizabeth Williamson, professor of biostatistics and health data science2,
- Kieran Brack, senior trial manager3,
- Danielle Beaumont, senior trial manager3,
- Alexander Perkins, research fellow2,
- Andrew Thayne, data assistant3,
- Haleema Shakur-Still, professor of global health3,
- Ian Roberts, professor in epidemiology3,
- Danielle Prowse, data manager3,
- Ben Goldacre, senior clinical research fellow4,
- Tjeerd van Staa, professor in health e-research5,
- Thomas M MacDonald, professor of clinical pharmacology6,
- Jane Armitage, professor of clinical trials and epidemiology7,
- Jon Wimborne, general practitioner8,
- Paula Melrose, research nurse8,
- Jayshireen Singh, primary care research nurse9,
- Lucy Brooks, research nurse10,
- Michael Moore, professor of primary healthcare research11,
- Maurice Hoffman, lay member of the trial steering committee12,
- Liam Smeeth, professor of clinical epidemiology1
- on behalf of the StatinWISE Trial Group
- Correspondence to: L Smeeth, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK email@example.com
- Accepted 10 December 2020
Objective To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins.
Design Series of randomised, placebo controlled n-of-1 trials.
Setting Primary care across 50 sites in the United Kingdom, December 2016 to April 2018.
Participants 200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms.
Interventions Participants were randomised to a sequence of six double blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo.
Main outcome measures At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale (0-10). The primary analysis compared symptom scores in the statin and placebo periods.
Results 151 participants provided symptoms scores for at least one statin period and one placebo period and were included in the primary analysis. Overall, no difference in muscle symptom scores was found between the statin and placebo periods (mean difference statin minus placebo −0.11, 95% confidence interval −0.36 to 0.14; P=0.40)). Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long term treatment with statins.
Conclusions No overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo was found in participants who had previously reported severe muscle symptoms when taking statins. Most people completing the trial intended to restart treatment with statins. N-of-1 trials can assess drug effects at the group level and guide individual treatment.
Trial registration ISRCTN30952488, EUDRACT 2016-000141-31, NCT02781064.