Approach to the Patient Who Is Intolerant of Statin Therapy

Abstract

Myopathy occurs in approximately 10% of statin-treated patients and is most commonly manifested by myalgias with or without plasma creatine kinase (CK) elevations. Predisposition exists in patients treated with high doses of potent statins and those who are older, female, have a genetic predisposition, and when statins are coadministered with drugs that compete with or inhibit drug metabolism. In symptomatic patients, CK levels may assist in guiding management. If less than five times the upper limit of normal, the existing statin should be titrated to achieve cholesterol goals and the CK repeated when symptoms appear or worsen. In patients with moderate to severe symptoms and any patient with CK elevated to more than 5-fold the upper limit of normal, the statin should be stopped. Once asymptomatic and CK is reduced (if elevated previously), cholesterol goals can be approached by: 1) a different statin (e.g. fluvastatin or pravastatin), starting with a low dose and titrating up; 2) an alternate daily or weekly more potent statin (e.g. rosuvastatin or atorvastatin); or 3) the combination of the lowest tolerated statin with a cholesterol absorption inhibitor (ezetimibe) and/or bile acid sequestrant. Over-the-counter preparations, e.g. red yeast rice, containing natural statin-like agents, or plant sterols can also lower cholesterol. These, however, have limited efficacy to achieve targeted cholesterol levels for most patients. In patients without CK elevations and symptoms, progress can be followed clinically, but in patients who show CK elevations, CK should be monitored. At present, the superiority of one approach has not been demonstrated, and the need for clinical trials in well-characterized patients with statin intolerance cannot be dismissed.