Study finds no difference in muscle symptom scores between statin, placebo

Three months after 200 primary care patients in the U.K. who previously reported muscle symptoms from statins underwent a series of randomized, placebo-controlled, n-of-one trials, about two-thirds said they planned to restart statin treatment.

A recent study found no overall effect of atorvastatin on the frequency or severity of muscle symptoms.

To assess the effect of statins on muscle symptoms in patients who had reported them, researchers conducted StatinWISE (Statin Web-based Investigation of Side Effects), a series of randomized, placebo-controlled, n-of-one trials at 50 primary care sites in the U.K., from December 2016 to April 2018. Participants included 200 patients who had recently stopped or were considering stopping treatment with statins due to muscle symptoms. They were randomized to a sequence of six double-blinded treatment periods, lasting two months each, of atorvastatin (20 mg/d) or placebo sent by mail. At the end of each treatment period, participants rated their muscle symptoms for the last seven days on a visual analog scale (0 to 10) online, by phone, or by mail. The primary analysis compared symptom scores between the statin and placebo periods. A secondary outcome was whether the participant had restarted or intended to restart statin treatment at three months after the end of the final treatment period. Results were published online on Feb. 24 by The BMJ.

A total of 151 participants (76%) provided scores for at least one statin period and one placebo period and were included in the primary analysis. These patients contributed 2,638 symptom score measurements during 392 statin periods and 2,576 measurements during 383 placebo periods. The mean muscle symptom score was lower during statin treatment periods (mean score, 1.68; SD, 2.57) than during placebo periods (mean score, 1.85; SD, 2.74). Overall, there was no difference in the scores between the statin and placebo periods (mean difference for statin minus placebo, −0.11; 95% CI, −0.36 to 0.14; P=0.40). Of 113 participants who completed all six treatment periods, 74 (66%) said that they had already resumed or intended to resume taking statins. Seventeen of 113 (15%) had a mean muscle symptom score at least one unit higher during the statin than the placebo periods and were informed that statins might be contributing to their muscle symptoms. Of these 17 patients, nine (53%) said they planned to restart treatment with statins. Of the remaining 96, 65 (68%) said they planned to restart treatment with statins.

Among other limitations, nearly half of patients did not complete the whole trial, and 49 patients did not provide sufficient data to contribute to the primary analysis, the study authors noted. However, they added that adherence was similar for the statin and placebo periods and that the trial was adequately powered to account for this level of attrition.

In a linked opinion article, the authors said that while n-of-one trials may be useful in primary care, they encountered challenges that would need to be overcome before routine implementation. “Rolling out a n-of-1 service into routine clinical practice would inevitably have its challenges (especially around the provision of placebos and the requirement to monitor adverse effects), but it would be a great benefit to individual patients and to the [National Health Service],” they wrote. “The n-of-1 design would be useful beyond the context of statins and muscle symptoms, and could be used for many reversible short term drug effects—both beneficial and harmful—where uncertainty exists.”