Statin Muscle Symptom Risk Overblown, Does Not Outweigh CV Benefits, CTT Study Shows

Colin Baigent, MBCHB

A meta-analysis presented at the European Society of Cardiology (ESC) Congress 2022 provides evidence demonstrating the cardioprotective benefits of statin therapy far outweigh the potential risk of muscle symptoms reported in previous data.

An analysis of data from 23 trials within the Cholesterol Treatment Trialists’ (CTT) Collaboration, results of the study suggest the excess risk for muscle symptoms observed with statins was less than 1%, with more than 90% of muscle symptoms reported not attributable to statin therapy.

“For most people taking a statin, any muscle-related symptoms they experience are not likely to be caused by the drug. The known protective effects of statins against cardiovascular disease greatly exceed the slightly increased risk of muscle symptoms. For example, for every 1,000 people taking a moderate intensity statin, the treatment would cause 11 generally mild episodes of muscle pain or weakness in the first year with no significant excess in subsequent years,” said Colin Baigent, BMBCh, director of the Medical Research Council Population Health Research Unit at the University of Oxford,in a statement. “Over a 5-year period, statins typically prevent 50 major vascular events in those with pre-existing vascular disease, and 25 major vascular events in those with no pre-existing vascular disease, with longer treatment yielding larger benefits.”

Although regarded among cardiologists, as well as clinicians in other specialties, as being among the most important and impactful advances in medicine since the 1980s, statins have come under fire for purported side effects, with a potential for muscle symptoms among the most reported side effects of use. Despite the results of N-of-1 studies and other research, concerns surrounding the impact of statin use on muscle symptoms remain.

With an interest in estimating the risk of muscle symptoms with use of statins, investigators designed the current study as a meta-analysis of double-blinded trials with populations of 1000 patients or greater and a minimum follow-up of 2 years within the CTT. From their search investigators identified 23 double-blind trials for inclusion in their meta-analysis. Of these, 19 compared statins against placebo and 4 compared statins against a less intensive statin. From trials comparing statin against placebo, the overall population was 123,940 participants, the mean age was 63 (SD, 8) years, 28% were women, 48% had vascular disease, and the median duration of follow-up was 4.3 years. From trials comparing statin use against a less intensive statin, the overall population was 30,724 participants, the mean age was 62 (SD, 9) years, 26% were women, 100% of had known vascular disease, and the median duration of follow-up was 4.9 years.

In trials comparing statin use against placebo, analysis suggested 27.1% (n=16,835) of the statin group and 26.6% (n=16,446) of the placebo group reported muscle pain or weakness (RR, 1.03 [95% CI, 1.01-1.06]). When assessing reports within the first year, investigators noted a 7% relative increase in reports of muscle pain or weakness among those allocated to statin therapy rather than placebo, which investigators also pointed out corresponded to an absolute excess rate of 11 (95% CI, 6-16) per 1000 person-years. Analysis of the remainder of the follow-up data provided no evidence of any excess risk. According to investigators, only about 1-in-15 reported instances of muscle pain or weakness were attributable to statin therapy.

In trials comparing statin use against less intensive statin therapy, results indicated use of high-intensity regimens, which was defined as atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily, was associated with a larger relative increase in the rate of muscle pain or weakness compared to more moderate intensity regimens, with rate ratios of 1.08 (95% CI, 1.04-1.13) and 1.02 (95% CI, 1.00-1.05), respectively.

“Muscle symptoms such as pain or weakness were experienced by similar numbers of people in the statin and placebo groups. Statins were not the cause of muscle pain in more than 93% of patients who reported symptoms," Baigent added. "Statin therapy marginally increased the frequency, but not the severity, of muscle-related symptoms. The small excess risk of muscle symptoms occurred principally during the first year after commencing therapy.”

This study, “CTT meta-analysis of the effects of statins on muscle symptoms,” was presented at ESC Congress 2022.