Study Questions Validity of Link Between Statin Use and Muscle-Related Adverse Events

Statin use was not associated with muscle-related adverse effects (AEs) when patients were not aware that they were taking them, illustrating the “nocebo effect,” according to the results of a recent study.

Noting that statins are rarely associated with muscular AEs in blinded randomized controlled trials, but are more often associated with AEs in observational studies, researchers conducted a study of 10,180 patients, aged 40 to 79 years, who had hypertension, at least 3 other cardiovascular risk factors, and fasting total cholesterol concentrations of 6.5 mmol/L or lower, who were not taking a statin or fibrate and had no history of myocardial infarction.
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The participants were randomly assigned to either atorvastatin 10 mg daily or matching placebo during the blinded phase of the study, and during the subsequent non-randomized non-blinded extension phase, all patients were offered atorvastatin 10 mg daily open label.

During the blinded phase, muscle-related AEs and erectile dysfunction were reported in similar numbers between the statin and placebo groups, and sleep disturbances occurred significantly less in patients taking the statin. More renal and urinary AEs were also reported among the statin group. No significant differences were reported in all other AEs.

During the non-blinded phase, muscle-related AEs were reported at a significantly higher rate in patients taking statins than in those not taking statins, while no significant differences were noted for all other AEs, except for musculoskeletal and connective tissue disorders and blood and lymphatic system disorders, which were more common in statin users.

“These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects,” the researchers concluded.

—Michael Potts

Reference:

Gupta A, Thompson D, Whitehouse A, et al, on behalf of the ASCOT Investigators. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase [published online May 2, 2017]. Lancet. doi: dx.doi.org/10.1016/S0140-6736(17)31075-9.