Media release

From: The Lancet

The Lancet: Statins do not commonly cause muscle pain, best analysis to date confirms

• Meta-analysis of data from 155,000 patients from 23 randomised double-blind trials suggests that, when a patient reports muscle symptoms whilst taking a statin, there is a less than 10% chance that the symptom is caused by the statin.
• The small increased risk of muscle symptoms due to statin therapy was mostly observed within the first year of treatment. After the first year there was no significant increase in the risk of reporting muscle pain.
• The authors highlight that the risk of muscle symptoms caused by statins should be considered alongside the cardiovascular benefits of statin therapy.
• In light of their findings, the researchers call for a review of the recommended strategies for managing muscle pain during statin therapy, and a revision of the information in the medication label for statins.

In over 90% of cases, statin therapy is not likely to be the cause of muscle pain in a person taking statins, according to the most comprehensive analysis of the risks to date, published in The Lancet..

Statin therapy is widely prescribed as an effective prevention of cardiovascular disease, but there have been widespread concerns that statins may frequently cause muscle pain or weakness.

The new study looks at individual patient data to provide a more detailed analysis of the risk of muscle pain caused by statins than has previously been possible and concludes that this is low and does not outweigh the benefits of statin therapy.

“The idea that statins may cause frequent muscle pain has been a persistent belief among some patients and clinicians, however our study confirms that the statin is rarely the cause of muscle pain in those taking statins.” says Professor Colin Baigent, Director of the Medical Research Council Population Health Research Unit at the University of Oxford, and joint lead author of the study. “These findings suggest that if a patient on statins reports muscle pain, then it should first be assumed that the symptoms are not due to the statin and are most likely due to other causes. Statin therapy should continue until other potential causes have been explored. Additionally, in light of our analysis, we believe there is a need to revise the information in the medication label for statins to clarify that most muscle pain experienced during statin therapy is not due to the statins.” [1]

The authors analysed data from 155,000 patients from 23 trials of statin therapy; each trial had over 1,000 patients and a follow-up time of over two years and had a double-blind comparison of statin vs placebo, or of a more or less intensive statin regimen. Individual patient data on all adverse events were studied which allowed a more detailed analyses of risk. The authors compared rates of muscle symptoms in the group undergoing statin treatment with the placebo group to calculate the proportion of symptoms directly caused by the statin therapy.

The meta-analysis found that, among 19 placebo-controlled trials with an average follow up period of four years, 27.1% of patients who were given statins (16,835/62,028) reported muscle pain or weakness, compared to 26.6% of those who were given the placebo (16,446/61,912). During the first year of treatment, statin therapy produced a 7% relative increase in muscle pain or weakness compared to placebo, suggesting that only one in 15 of these muscle-related reports by patients given statins were due to the statin. The absolute excess risk of muscle symptoms due to a statin was 11 per 1,000 patients treated during the first year. After the first year of treatment, there was no significant difference in reports of muscle pain or weakness between those given statins and those given the placebo.

The researchers also looked at four randomised double-blind trials of more intensive versus less intensive statin therapy. The data from these trials were analysed alongside the placebo trials to see if the dose of statin made a difference to the risk of muscle pain caused by the statin. The study did not find any clear evidence of a dose-response relationship; however, they did observe in the first year of treatment that higher intensity statins caused a greater increase in the risk of muscle pain caused by statins compared to placebo (an 11% increase in risk) than moderate-intensity statin treatment compared to placebo (a 6% increase in risk). They also found that after one year the high intensity statin treatments produced a 5% relative increase in muscle pain or weakness compared to placebo. This suggests that not only do high-intensity statin treatments lead to larger risks of muscle symptoms in the first year than moderate-intensity statins, but that there may be a persisting low risk of such symptoms beyond this time.

The analysis also found that the small proportion of patients who did experience muscle symptoms caused by statins did not usually stop their statin treatment. This implies that most cases of muscle pain or weakness caused by a statin were clinically mild.

“Our research shows that whilst people on statin therapy may develop muscle symptoms, it is important to note that people not on statins also commonly get such symptoms.” Says Dr Christina Reith, Senior Clinical Research Fellow at Oxford Population Health and joint lead author of the study. “For people on statins who do develop muscle symptoms, most of the time statins will not be the cause. We hope that these results will help doctors and patients to make informed decisions about whether to start or remain on statin therapy, bearing in mind its known significant benefits in reducing the risk of cardiovascular disease.”

The authors acknowledge some limitations to their study including a lack of consistently available data about whether muscle events led to discontinuation of treatment. Additionally, there was no reliable information about some relevant comorbid conditions or other medications that may affect the risk of experiencing symptoms.

Writing in a linked Comment, Professor Maciej Banach, Professor of Cardiology at the Medical University of Lodz (MUL), Lodz, Poland, who was not involved in the study, says: “The issue of statin-associated side effects has been discussed for at least 15-20 years and despite overwhelmingly reassuring data from RCTs, cohort studies and registries, side effects are still the main cause of statin nonadherence. In 2022, the problem does not arise from a lack of data, diagnostic criteria, effective therapies, or treatment recommendations; but from insufficient education both of physicians and patients. […] Based on these important results we should strongly emphasize that the small risk of muscle symptoms is insignificant in comparison with the high proven cardiovascular benefits of statins. Thus, we should not think about the possible side effects of statins before we start the treatment, and we should always start by considering how best to reduce CVD risk in our patients and begin optimal treatment accordingly, because in the end […] we can continue statin treatment in even 98% of our patients.”