Aernoud Fiolet

150 Chapter 5 D: Assessment of muscle symptoms Symptoms Biomarker Comment Muscle symptoms Normal CK Often called ‘myalgia’. May be related to statin therapy. Causality is uncertain in view of the lack of evidence of an excess of muscle symptoms in blinded randomized trials comparing statin with placebo. Muscle symptoms CK >ULN <4× ULN CK >4 <10× ULN Minor elevations of CK in the context of muscle symptoms are commonly due to increased exercise or physical activity, but also may be statin-related; this may indicate an increased risk for more severe, underlying muscle problems Muscle symptoms CK >10× ULN Often called myositis or ‘myopathy’ by regulatory agencies and other groups (even in the absence of a muscle biopsy or clinically demonstrated muscle weakness). Blinded trials of statin vs. placebo show an excess with usual statin doses of about 1 per 10 000 per year. Pain is typically generalized and proximal and there may be muscle tenderness and weakness. May be associated with underlying muscle disease. Muscle symptoms CK >40× ULN Also referred to as rhabdomyolysis when associated with renal impairment and/or myoglobinuria. None CK >ULN <4× ULN Raised CK found incidentally, may be related to statin therapy. Consider checking thyroid function or may be exercise-related. None CK >4× ULN Small excess of asymptomatic rises in CK have been observed in randomized blinded trials in which CK has been measured regularly. Needs repeating but if persistent, then clinical significance is unclear. Based on the European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management of Statin-associated muscle symptoms from 2015. 4