Effects of nocebo and drusebo in determining statin-induced muscle symptoms

Abstract

Statins represent an important class of cardiovascular drugs for the prevention of atherogenic complications. However, despite the effectiveness of statins, non-adherence and discontinuation of therapy with these drugs is a problem worldwide. Reasons for not using statins in patients at high CV risk include statin-associated muscle symptoms (SAMS), which are not usually associated with significant elevations of serum creatine kinase. SAMS are the most common side effects of statins: 3–5% in RCTs, 15–20% in observational studies, and 60% in patient surveys. This range is possibly due to misinterpretation of symptoms, as well as patients’ expectation of harm from statin treatment (“statin fear”). The article highlights the problem of studying the role of nocebo and drusebo effects for SAMS, presents differences in definitions and methods of detection. The concept of the drucebo effect was proposed by the International Lipid Expert Group (ILEP, 2018) as a harm to the patient, unrelated to the pharmacological action of the drug (negative effect of the drucebo). The results of studies and meta-analyses evaluating the effects of nocebo and drusebo for SAMS are presented, in which no difference was found in the frequency and severity of muscle symptoms between statin and placebo; the nocebo rate was 90% of the statin effect, and the contribution of the drusebo effect to SAMS and statin discontinuation ranged from 38 to 78%. Also presented are current international guidelines and principles of patient management aimed at preventing discontinuation of statin use in connection with SAMS.