Step‐by‐step diagnosis and management of the nocebo/drucebo effect in statin‐associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP)

Abstract

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin-associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3-5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)-what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real-world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step-by-step patient-centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long-term compliance with lipid-lowering therapy.

Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials

“…Currently, the management of patients reporting muscle symptoms while taking statin therapy is challenging, since the belief that statin therapy often causes such symptoms is encouraged by drug labelling and other misleading sources of information (contributing to the so-called nocebo or drucebo effect, where negative expectations can lead to perceived adverse effects). 8 , 53 By contrast, our results confirm that, in the majority of cases, statin therapy is not likely to be the cause of muscle pain in a person taking statin therapy. This finding is particularly true if the treatment has been well tolerated for a year or more before developing symptoms; but, even during the first year of a moderate-intensity statin regimen, it is likely to be the cause in only approximately one in 15 patients who report muscle symptoms, rising to approximately one in 10 in those who are taking a more intensive regimen.…”

Post-discharge and long-term follow-up after an acute coronary syndrome: International Collaborative Group of CNCF position paper.

“…The early consultation provides an ideal time to check for – and manage – any adverse reactions (e.g. myalgia, nuisance bleeding or tiredness) that can reduce adherence to treatment [ 9 , 10 ].…”

“…Based on the most recent data, the worldwide prevalence of statin intolerance is 9.1% [ 59 – 64 ]. Patients who report symptoms of statin intolerance should always be diagnosed based on the approved definitions [ 9 ] assessed using the statin associated muscle symptoms clinical index (SAMS-CI) [ 65 ]. Recent data suggest that nocebo effects might be responsible for even 50–70% of the cases [ 66 ].…”

“…Recent data suggest that nocebo effects might be responsible for even 50–70% of the cases [ 66 ]. The ESC/European Atherosclerosis Society (EAS) have published joint recommendations for the management of myalgia with statins using a clinical algorithm [ 9 , 64 ]. Bempedoic acid, besides innovative drugs associated with PCSK9 inhibition, alone or in fixed combination with ezetimibe, is a very effective option in patients with confirmed statin intolerance [ 9 , 67 ].…”

Which patients at risk of cardiovascular disease might benefit the most from inclisiran? – The expert opinion of the Polish experts. The compromise between EBM and possibilities in healthcare.

“…– There is a great need to have a clear definition of statin intolerance based on existing recommendations, including the most recent guidelines of six Polish scientific societies [ 15 ] and recent recommendations of the International Lipid Expert Panel (ILEP) [ 27 ]. We, therefore, recommend using the practical definition of statin intolerance as ‘documented intolerance to at least two statins, including the second statin with the lowest dose recorded, for a period of at least 3 months’;…”