Clever trial design gets patients back on statins: the SAMSON trial

 

For patients who had discontinued statin therapy due to side effects, 90% of the symptom burden elicited by a statin challenge was also elicited by placebo [1]. This convinced half of the study subjects to (successfully) restart statin therapy, according to results from the SAMSON trial.

Dr James Howard (Imperial College London, UK) presented the trial data, which were simultaneously published in the New England Journal of Medicine [1,2]. The highly anticipated SAMSON trial had a very original design. “This trial was designed to clarify the mystery as to why so many of our patients suffer side effects while taking statins, and yet randomised controlled trials including placebo show a similar risk of side effects, whether patients take statin or placebo tablets,” Dr Howard explained. The N-of-1 trial included 60 patients, all of whom had previously stopped statin treatment due to side effects. They were randomised to alternating 1-month periods of either 20 mg atorvastatin, placebo, or an empty pill bottle in a blinded fashion for 1 year. Each patient received 4 bottles containing atorvastatin, 4 bottles containing placebo, and 4 empty bottles. Patients scored their symptom intensity daily on a 100-point scale using a smartphone app.

Mean symptom intensity was significantly higher during the placebo months (15.4; 95% CI 12.1–18.7) and statin months (16.3; 95% CI 13.0–19.6) compared with the no-tablet months (8.0; 95% CI 4.7–11.3) (both P<0.0005). However, there was no significant difference between placebo and the statin (P=0.39). Pooling the results across patients, 90% of symptoms could be attributed to the nocebo effect.

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 ≥6 months), and another 4 subjects were considering restarting. “SAMSON leaves no doubt that patients really do experience side effects from statin tablets”, Dr Howard commented. “However, these effects are not caused by the statin molecules, but by the act of taking the tablet.”

 

1. 
   
   1. 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. 04, AHA Scientific Sessions 2020, 13-17 Nov.
   2. Wood F, et al. New Engl J Medicine 2020;383:2182-2184.

 



Posted on 17 February 202125 March 2024