Not Sure If the Patient Tolerates Statins? Consider an N-of-1 Trial

Diagnosing statin-related myalgia depends largely on patients' and physicians' perceptions of what's causing muscle symptoms during open-label therapy. In N-of-1 trials, each patient serves as his or her own control, thus allowing a randomized, multiple-crossover, blinded comparison of active treatment and placebo. Researchers have now conducted n-of-1 trials in eight patients (mean age, 66) who met criteria for statin-related myalgia and had high-risk Framingham scores. At baseline, the participants had a mean LDL level of 128 mg/dL, had tried a median of three statins, and still had mild myalgia symptoms 3 months after discontinuing all statins.

During the 3-week active-treatment phases, overall adherence to a rechallenge with the previously tried statin (mostly atorvastatin, pravastatin, or rosuvastatin) was 92%. Seven of eight patients showed neither a clinically nor a statistically greater level of myalgia symptoms with statin treatment than with placebo; one patient's on-statin symptoms reached clinical but not statistical significance.

In a combined analysis of the eight trials, patients' myalgia symptoms and their symptom-specific and pain-interference scores did not differ significantly between the statin-use and placebo-use periods. Compared with placebo, statin treatment was associated with greater pain severity that reached statistical but not clinical significance. Of seven patients whose end-of-trial LDL levels warranted statin use, five resumed and continued to receive statin therapy for a median of 10 months.