1st Cardiology Department, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece.
Drug Saf. 2010 Mar 1;33(3):171-87. doi: 10.2165/11319380-000000000-00000.
HMG-CoA reductase inhibitors ('statins') represent the most effective and widely prescribed drugs currently available for the reduction of low-density lipoprotein cholesterol, a critical therapeutic target for primary and secondary prevention of cardiovascular atherosclerotic disease. In the face of the established lipid lowering and the emerging pleiotropic properties of statins, the patient population suitable for long-term statin treatment is expected to further expand. An overall positive safety and tolerability profile of statins has been established, although adverse events have been reported. Skeletal muscle-related events are the most common adverse events of statin treatment. Statin-induced myopathy can (rarely) manifest with severe and potentially fatal cases of rhabdomyolysis, thus rendering the identification of the underlying predisposing factors critical. The purpose of this review is to summarize the factors that increase the risk of statin-related myopathy. Data from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects were reviewed. Briefly, the epidemiology, clinical spectrum and molecular mechanisms of statin-associated myopathy are discussed. We further analyse in detail the risk factors that precipitate or increase the likelihood of statin-related myopathy. Individual demographic features, genetic factors and co-morbidities that may account for the significant interindividual variability in the myopathic risk are presented. Physicochemical properties of statins have been implicated in the differential risk of currently marketed statins. Pharmacokinetic interactions with concomitant medications that interfere with statin metabolism and alter their systemic bioavailability are reviewed. Of particular clinical interest in cases of resistant dyslipidaemia is the interaction of statins with other classes of lipid-lowering agents; current data on the relative safety of available combinations are summarized. Finally, we provide an update of current guidelines for the prevention and management of statin myopathy. The identification of patients with an increased proclivity to statin-induced myopathy could allow more cost-effective approaches of monitoring and screening, facilitate targeted prevention of potential complications, and further improve the already overwhelmingly positive benefit-risk ratio of statins.
羟甲基戊二酰辅酶 A 还原酶抑制剂（“他汀类药物”）是目前降低低密度脂蛋白胆固醇最有效和广泛应用的药物，胆固醇是心血管动脉粥样硬化疾病一级和二级预防的关键治疗靶点。鉴于他汀类药物已有的降脂作用和新出现的多种作用，预计适合长期他汀类药物治疗的患者人群将进一步扩大。他汀类药物的总体安全性和耐受性良好，但也有不良反应报告。他汀类药物治疗相关的骨骼肌事件是最常见的不良反应。他汀类药物引起的肌病（罕见）可表现为严重且潜在致命的横纹肌溶解症，因此确定潜在的诱发因素至关重要。本文综述了增加他汀类药物相关肌病风险的因素。我们查阅了已发表的临床试验、荟萃分析、上市后研究、自发报告系统和罕见效应病例报告的数据。简要讨论了他汀类药物相关肌病的流行病学、临床谱和分子机制。我们进一步详细分析了引发或增加他汀类药物相关肌病可能性的危险因素。我们介绍了可能导致个体间肌病风险存在显著差异的个体人口统计学特征、遗传因素和合并症。他汀类药物的物理化学特性与目前市场上销售的他汀类药物的不同风险相关。我们还讨论了与他汀类药物代谢相互作用并改变其全身生物利用度的伴随药物的药代动力学相互作用。在耐药性血脂异常的情况下，特别具有临床意义的是他汀类药物与其他降脂药物类别的相互作用；总结了现有可用组合的相对安全性的最新数据。最后，我们更新了他汀类药物肌病的预防和管理指南。识别易发生他汀类药物诱导性肌病的患者，可以更有效地进行监测和筛查，有针对性地预防潜在并发症，并进一步提高他汀类药物已有的压倒性积极获益风险比。
