Patients who had previously quit taking a statin due to side effects were randomized to alternating 1-month periods of either 20 mg atorvastatin, placebo, or an empty pill bottle in a blinded fashion for 1 year. They performed daily symptom checks on a smartphone app. When provided with the data showing that their side effects while on placebo were as bad as those reported on statins, half the patients resumed their lipid-lowering statin treatment.
Dr. James Howard (Imperial College London, UK) presented the trial data, which was simultaneously published in the New England Journal of Medicine [1,2]. The N-of-1 trial included 60 patients, all of whom had previously stopped statin treatment due to side effects. Patients each received 4 bottles containing atorvastatin at a dose of 20 mg, 4 bottles containing placebo, and 4 empty bottles; each bottle was to be used for a 1-month period according to a random sequence provided to each patient. Participants scored their symptom intensity on a 100-point scale using a smartphone app daily throughout the year.
According to expectation, participants scored their mean symptom intensity higher when taking either placebo or the statin, as opposed to months without a pill (8.0 during no-pill months compared with 15.4 on placebo and 16.3 on the statin; both P<0.001). However, there was no significant difference between placebo and the statin (P=0.39). Pooling the results across patients, 90% of the symptoms could be attributed to the so-called nocebo effect (0.90 ratio of placebo-taking months vs no-pill months/statin-taking months vs no-pill months).
After the trial period, the data was provided to the participants. Showing the patients that most of the side effects they had attributed to a statin were equally evident while on placebo convinced 30 of the 60 subjects to successfully restart statin therapy (for at least 6 months), and another 4 subjects were considering restarting. In conclusion, for patients who had discontinued statin therapy because of side effects, 90% of the symptom burden elicited by a statin challenge was also elicited by placebo.
- Howard J, et al. A Three-Arm N-of-1 Trial With Statin, Placebo and Tablet Free Periods, to Verify Side Effects and Identify Their Cause: The SAMSON Trial. LBS.04, Virtual AHA Scientific Sessions 2020, 13-17 Nov.
- Wood F, et al. N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects. New Engl J Medicine 2020; Nov 15.DOI: 10.1056/NEJMc2031173.