Statin intolerance

Am J Cardiol. 2014 May 15;113(10):1765-71. doi: 10.1016/j.amjcard.2014.02.033. Epub 2014 Mar 2.


The term statin intolerance refers to an inability to use statins because of muscle symptoms or elevated creatine kinase, and the major diagnostic challenge is to unambiguously link these to statin use. Roughly 5% to 10% of statin users develop statin intolerance, and because statin use is expected to increase--especially after recent updated guidelines have expanded the statin benefit groups--adverse effects from statins will become a growing issue. Unfortunately, the pathophysiology--and even the terminology--of statin-related muscle injury lacks clarity. Several risk factors have been identified, including advanced age, family history of myopathy and statin dose; many cases manifest only after patients are administered an interacting medication (e.g., azole antifungals, cimetidine, clarithromycin, erythromycin and cyclosporine). The diagnosis of myopathy remains challenging, especially because some patients can have normal serum creatine kinase levels despite demonstrable weakness and muscle biopsy-proven statin-induced myopathy. A statin withdrawal and rechallenge helps patients distinguish whether their myalgia symptoms are because of statins, but, in at least 1 clinical trial, even 5% of placebo-treated patients developed myalgias during a controlled withdrawal and rechallenge. No consensus exists for management of patients with statin intolerance. Many patients can eventually tolerate a statin but often at suboptimal doses. A subset of patients do well with nondaily regimens such as every other day or once weekly dosing. Some patients cannot tolerate statins at all, requiring nonstatin lipid-lowering medications--the benefit of which remains unclear with regard to preventing atherosclerotic events. Ultimately, statin intolerance undermines the drug adherence that is critical for achieving the benefits of lifelong lipid-lowering therapy. In conclusion, statin myopathy is a common challenge in lipid management, and further work is needed to establish a standard diagnostic criterion as well as treatment algorithms.

Publication types

  • Review

MeSH terms

  • Creatine Kinase / blood*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipidemias / blood
  • Hyperlipidemias / drug therapy
  • Muscular Diseases / blood
  • Muscular Diseases / chemically induced*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Creatine Kinase