Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas.
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.
他汀类药物不耐受是指由于肌肉症状或肌酸激酶升高而无法使用他汀类药物，主要的诊断挑战是明确将这些症状与他汀类药物的使用联系起来。大约 5%至 10%的他汀类药物使用者会出现他汀类药物不耐受，而且由于预计他汀类药物的使用量会增加——尤其是最近更新的指南扩大了他汀类药物的受益人群后——他汀类药物的不良反应将成为一个日益严重的问题。不幸的是，他汀类药物相关肌肉损伤的病理生理学——甚至术语——仍缺乏明确性。已经确定了一些风险因素，包括年龄较大、家族性肌病病史和他汀类药物剂量；许多病例仅在患者接受相互作用药物（如唑类抗真菌药、西咪替丁、克拉霉素、红霉素和环孢菌素）治疗后才会出现。肌病的诊断仍然具有挑战性，尤其是因为一些患者尽管有明显的无力和肌肉活检证实的他汀类药物诱导的肌病，但血清肌酸激酶水平可能正常。他汀类药物停药和再挑战有助于患者区分其肌痛症状是否是由他汀类药物引起的，但在至少一项临床试验中，即使是 5%的安慰剂治疗患者在对照停药和再挑战期间也出现了肌痛。对于他汀类药物不耐受患者的管理，目前尚无共识。许多患者最终可以耐受他汀类药物，但通常剂量不足。有一部分患者使用非每日方案（如隔日或每周一次给药）效果良好。有些患者根本不能耐受他汀类药物，需要使用非他汀类降脂药物——但关于预防动脉粥样硬化事件，其益处仍不清楚。最终，他汀类药物不耐受破坏了实现终身降脂治疗获益所需的药物依从性。总之，他汀类药物肌病是脂质管理中的常见挑战，需要进一步努力建立标准的诊断标准和治疗方案。
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