Muscle Symptoms Associated with Statins: A Series of Twenty Patients

Abstract

The aim of this study was to examine the clinical profile of statin-induced myalgia in patients with no apparent predisposing factors. Patients who reported muscle complaints that limited daily functioning during statin use were prospectively identified among the patients of Kuusankoski District Hospital and its catchment area, a population of about 100,000, between January 2003 and July 2004. Twenty patients in whom the muscle complaints were probably attributable to the use of a statin were included in this series. There were no cases of severe myopathy or rhabdomyolysis, and the highest creatine kinase value observed was only about 1900 U/l. Of the 18 patients that were evaluable for creatine kinase level, 5 (28%) did not exhibit elevation of creatine kinase and 6 (33%) showed a minor increase only. Following discontinuation of the statin, resolution of symptoms and normalisation of creatine kinase occurred in 11 of the 13 patients with elevated creatine kinase value as well as muscle complaints. Statins may cause clinically important muscle symptoms without inducing a marked creatine kinase elevation.Statins are well established as agents that reduce serum cholesterol concentrations and thereby decrease cardiovascular morbidity and mortality. Myopathy is one of the few serious adverse effects associated with the use of statins (Omar et al. 2001;Evans & Rees 2002;Thompson et al. 2003). Myopathy is usually defined as a proximal or generalised pain and/or weakness in skeletal muscles and a creatine kinase value higher than 10 times the upper limit of the normal range. Statin-induced myopathy can progress to rhabdomyolysis which can result in renal failure and death (Omar et al. 2001;Evans & Rees 2002;Thompson et al. 2003).Although the incidence rate of severe myopathy is very low, this adverse drug effect has considerable clinical importance in light of the widespread and expanding use of statins. Little is known about the molecular mechanisms of statin-associated myopathy. One popular view is that myopathy is associated with inhibition of HMG-CoA reductase in the muscle cells, which leads to decreased levels of cholesterol precursors and other products produced from mevalonic acid that are involved in posttranslational modification of essential regulatory proteins (Christians et al. 1998;Corsini et al. 1999;Liao 2002). The fact that statin myopathy is a much more rare event in clinical trials than in primary care settings may be explained by control of factors predisposing to myopathy and regular follow-up in trial patients (Thompson et al. 2003). The skeletal muscle toxicity of statins is at least partly dose-and concentration-dependent and the incidence of myopathy is considerably higher when high doses of statins are used or during concomitant use of agents that increase plasma statin concentrations (Davidson et al. 1997;Omar et al. 2001;Evans & Rees 2002;McKelvie & Dennett 2002). Drug interactions and other predisposing factors can be identified in many reported cases of severe myopathy. This stu...

Necrotizing autoimmune myopathy

“…b Creatine kinase tends to be in the very high range, from 3000-25000 IU/L, with a mean of 12900 IU/L [3]. In statin-related NAM, the creatine kinase has also been found in the high range of 958-45000 U/L [24], with the majority between 3000-8000 U/L, compared with likely a lower creatine kinase level of less than 2000 U/L in those with the self-limited toxic myopathy [23].…”

“…NAM associated with statins is presumed to have an immunological basis, different from the toxic myopathy found in most statin-associated myopathies which is selflimited and recovers over weeks to months upon discontinuation of the statin [23,24]. Two studies [2 ,24] reported a series of patients in whom there was active myocyte necrosis, mostly with minor or absent inflammation, in whom the myopathy persisted or progressed despite cessation of the statin.…”

Statin Induced Myopathy and Myalgia: Time Trend Analysis and Comparison of Risk Associated with Statin Class from 1991–2006

“…Specifically, the READ classification does not necessarily correspond to disease entities, and additional work was necessary to define criteria for classes of adverse events such as myopathy, myalgia and myositis which were included in the analyses. Additionally we selected READ codes for creatinine kinase measurements and included cases who had elevations at >10 times the upper limit of normal 100 IU/ml in females and 150 IU/ml in males, although not all patients with myopathy have elevated CK values [21]. Codes included identifying co-morbidities and potential confounders (for example cases with codes for rheumatic diseases and steroid use were excluded).…”

Update on Toxic Myopathies

“…Although the vast majority of statin-associated myopathies resolve upon drug cessation [53,54], there is increasing recognition that in some cases muscle symptoms can persist or progress [55•, 56•, 57, 58]. These cases seem to fall into two categories.…”