The innovative and elegant SAMSON trial answers protracted questions primarily about the side effects of statins.
This has a big impact, as statins can be: Include The most studied class of all drugs. Over 130,000 patients are enrolled in placebo-controlled trials. result It consistently shows a 25% relative reduction in future cardiac events.
However, many patients discontinue the drug due to side effects, most often muscle pain. Large-scale observational studies 20% To 50% High incidence of muscle pain in statin users and non-users.
However, in a blinded randomized controlled trial (RCT), people taking statins almost the same Percentage of minor side effects when taking placebo.
One way to explain the discrepancy between observational studies and RCTs is that statin trials have a break-in period that excludes patients who report side effects.Another explanation is Nosebo effect— When negative expectations produce negative results.
Ann Italian group We publish one of the best examples of the Nosebo effect.They gave beta blockers Atenolol To three groups of men: one group was not informed, another was informed about the drug but not side effects, and the third group was informed about the possibilities. Erectile dysfunction.. The rates of erectile dysfunction in each group were 3%, 15%, and 31%, respectively.
Samsung trial
The SAMSON trial was announced at the 2020 American Heart Association (AHA) Scientific Sessions and at the same time. New England Journal of Medicine, James Howard and colleagues at Imperial College London tested the nosevo effect of statins.
They are so-called n-of-1 trial design Each patient acts as their own control. This design is nifty because it reflects what the clinician actually does. You start a drug and see if it makes a person feel better. If you’re not sure, stop, observe for a while, and then restart.
The main difference with SAMSON is that the patient and doctor were not informed of the treatment. In this study, 60 patients who had previously discontinued statins due to side effects were randomly assigned to a 12-month period consisting of no medication, placebo, and statins. All but 11 patients completed the 12-month study.
Patients recorded daily symptom intensity (0-100) with a smartphone app.
The main result of this study was the ratio of the intensity of excess symptoms caused by placebo to the intensity of excess symptoms caused by statins.
The graph below shows how the nocebo ratio was calculated. First, the researchers recorded the difference in symptom scores between not taking the pill and taking the placebo. This is the percentage of nosebo (that is, the negative effects of the negative expectations of the pill). Next, the authors recorded a symptom score from statins. This includes both the nosebo effect and the pharmacological effect of the drug.
Three main results
The mean symptom score for all patients was 8.0 in the pill-free month, 15.4 in the placebo month, and 16.3 in the statin month. Differences in symptom scores between placebo, statin, and pill-free months were very significant (P <.0001). However, the difference in symptom scores between placebo and statin months was not significant (P = .39). To calculate the nosebo effect, they divided the symptom score of the nosebo component by the ratio of statins to give a nosebo ratio of 0.9.
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Placebo Symptom Intensity (15.4) – Pillless Symptom Intensity (8.0) _____________________________________________________________ Statin Symptom Strength (16.3) – Pillless Symptom Strength (8.0) |
The authors conclude that taking statin tablets actually causes symptoms in patients. But decisively, 90% of these symptoms are also induced by placebopills.
Therefore, the side effects of statins are mainly caused by the act of taking pills. Six months after the end of the study, 30 of the 60 patients with personal results successfully resumed statins.
My comment
The results of the test should be considered in the context of previous data.
Prior to SAMSON, evidence of the nosebo effect of statins was strong. The most compelling statin RCT in this regard was the lipid-lowering group in the ASCOT trial. Atorvastatin Against placebo in 10,000 patients. ASCOT-LLA There was both a blind period and an unblind continuation. In the blind phase, there was no significant difference in muscle-related symptoms, but in the open phase, a significant number of patients in the statin group reported muscle symptoms.
We clinicians can use SAMSON results in the same way that Imperial College researchers used. Persuade some patients who were previously intolerant to statins to resume drugs that reduce heart events. That’s a big deal.
Another common message from SAMSON is for clinical trial physicians. If expectations can have such a big impact, imagine, for example, the difference in expectations of the next step arm. Atrial fibrillation Ablation vs. drug study.Or at Percutaneous coronary intervention (PCI) and medical therapy trial? Expectations are particularly relevant for measuring outcomes that are prone to subjective biases such as quality of life.
My favorite message from Samsung is how it informs the art of medicine. Experienced clinicians are well aware that getting the best results from a drug or procedure transcends pharmacology or physiology.That means managing Complex neurophysiology Of placebo and nosebo effects. Such effects can result from simple expectations of rewards and harm, social learning (think the Internet), and even Pavlov’s conditioning.
Clinicians must pay attention to our words and actions. Yes, we need to inform the patient, but it also makes sense to use all the tools of humanity to get positive results. The practice of showing beautiful angiographic results to patients and their families after PCI or being optimistic after AF ablation should not be underestimated.And there are all the reasons we should be when prescribing treatment positive..
The word “doctor” comes from the Latin verb “docere”. I save the SAMSON trial on my cell phone or computer and use it to teach patients about the power of expectation and the nosebo effect of statins. For example, if a patient reports a side effect of a statin, it is better to stop the SAMSON trial and teach about the nosebo effect if it emphasizes that the drug is causing the symptoms rather than reducing the dose of statin. is.
Still, empathy is still important. Patients who report side effects of statins have actual symptoms. They should not be rejected. SAMSON says it’s not just side effects Statins But from Statatin pill.
Samsung researchers beautifully show that being a healer means more than writing a prescription or moving a catheter. Thank you for that.
John Mandrola is a Medscape writer and podcaster practicing cardiac electrophysiology in Louisville, Kentucky. He supports a conservative approach to medical practice. He participates in clinical studies and frequently writes about the state of medical evidence.
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