Safety/tolerability RCT · J Am Coll Cardiol 2021
SAMSON trial
Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment.
The bottom line
In patients who had previously stopped statins due to side effects, symptom scores were equally elevated on statin and placebo compared with no treatment, indicating most statin-associated symptoms are a nocebo effect rather than a pharmacological effect of the drug.
Symptoms largely noceboUS status: US-approved
At a glance
- Medicine
- Atorvastatin 20 mg (4 months)
- Compared with
- Placebo (4 months) and no treatment/empty bottle (4 months)
- People
- 60
- Who took part
- Participants who had previously abandoned statin therapy due to side effects
- Design
- randomized crossover trial of statin, placebo, and no treatment (blinded, N-of-1 style design using 12 monthly bottles: 4 atorvastatin, 4 placebo, 4 empty)
- Follow-up
- 12-month protocol; 6 months post-trial follow-up
- Main question
- Daily symptom intensity score (scale 1-100) during statin, placebo, and no-treatment months
Main result
Mean symptom score 8.0 (95% CI: 4.7-11.3) in no-tablet months; 16.3 (95% CI: 13.0-19.6; P < 0.001) in statin months; 15.4 (95% CI: 12.1-18.7; P < 0.001) in placebo months; no difference between statin and placebo (P = 0.388); nocebo ratio 0.90
Other results
Neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo; stopping was no more frequent for statin than placebo (P = 0.173); subsequent symptom relief was similar between statin and placebo; at 6 months after the trial, 30 of 60 (50%) participants were back taking statins
In the trial's own words
“Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90.”
Quoted from the abstract of J Am Coll Cardiol 2021, checked word for word against PubMed. PubMed 34531021 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Statins
Common questions
What did the SAMSON trial find?
In patients who had previously stopped statins due to side effects, symptom scores were equally elevated on statin and placebo compared with no treatment, indicating most statin-associated symptoms are a nocebo effect rather than a pharmacological effect of the drug.
Who was in SAMSON?
60 people. Participants who had previously abandoned statin therapy due to side effects.
What was SAMSON's main result?
Mean symptom score 8.0 (95% CI: 4.7-11.3) in no-tablet months; 16.3 (95% CI: 13.0-19.6; P < 0.001) in statin months; 15.4 (95% CI: 12.1-18.7; P < 0.001) in placebo months; no difference between statin and placebo (P = 0.388); nocebo ratio 0.90
Related trials
- StatinWISE (2021)In patients with prior statin-associated muscle symptoms, atorvastatin 20 mg did not cause more muscle symptoms than placebo when tested in a blinded n-of-1 design, and most participants intended to resume statin therapy.
- LODESTAR (2023)In patients with coronary artery disease, rosuvastatin and atorvastatin provide similar long-term cardiovascular protection, but rosuvastatin carries a higher risk of new-onset diabetes requiring medication and cataract surgery.
- REPRIEVE (2023)In people with HIV at low-to-moderate cardiovascular risk, daily pitavastatin significantly reduced major adverse cardiovascular events compared with placebo, though with modestly more muscle symptoms and diabetes.
- SPORT (2023)In people with elevated ASCVD risk but no prior ASCVD, low-dose rosuvastatin (5 mg) lowered LDL-C far more than placebo or any of six common dietary supplements, which showed no significant LDL-C benefit over placebo.
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