Statins and muscle-related adverse events: Are subjective adverse events influenced by the nocebo effect?
In the case of statins, a high incidence of muscle pain and weakness had been reported in observational studies of patients who were aware they had been prescribed a statin and where there was no placebo control. In contrast, no significant difference in the incidence of muscle pain and weakness were reported in most double-blind, randomized, placebo-controlled trials.
The 10,180 patients with high cardiovascular (CV) risk enrolled in the ASCOT-LLA study were initially blinded as to whether they were randomized to atorvastatin 10 mg or placebo. In the subsequent non-blinded, non-randomized extension, all patients were offered open-label atorvastatin 10 mg daily.
Professor Sever explained that the high incidence of muscle-related symptoms reported in some studies of statins were not causally related. Rather, they are an example of the nocebo effect.
“During the blinded phase of ASCOT-LLA, the same proportion of patients reported muscle-related pain with the placebo [2.00%] compared with those receiving statins [2.03%]. However, once patients knew they were being administered statins in the non-blinded phase of the study, there was a significant increase in reports of these adverse events compared to the placebo group [1.26% vs 1.00%, respectively].”
Professor Sever commented that “while the reports of muscle-related adverse events may have been psychogenic and based on a patient’s expectations and perceptions, they still have the potential to produce measurable physiological changes.” This highlights the need for physicians to understand the context of, and appropriately interpret, clinical data so that accurate conclusions are made about the clinical effectiveness of treatments, such as statins.
In the clinical setting, the inappropriate interpretation of clinical study results, such as those regarding muscle pain and statin therapy, may ultimately result in patients becoming nonadherent to treatment. This may increase their risk of a major CV event, despite statins offering a potentially life-saving therapy. More broadly, these findings highlight how the nocebo effect, and biases in clinical trial design, have the potential to influence physician decisions and patient outcomes, particularly when treating an asymptomatic condition.
Click here to access the full article: Gupta A, et al. Lancet 2017;389:2473–2481
Click here to view the interview video with one of the authors –
Professor Peter Sever