Mukhtar Rasha Y A, Reckless John P D
Department of Endocrinology, Diabetes & Metabolism, Royal United Hospital, Bath, UK.
Curr Opin Lipidol. 2005 Dec;16(6):640-7. doi: 10.1097/01.mol.0000188414.90528.71.
Statins are well established as first-line agents for cholesterol lowering in cardiovascular disease, with accumulating evidence supporting their initiation and guidelines recommending treatment to lower LDL levels. Although generally well tolerated with few side effects, including headaches and gastrointestinal symptoms, concerns are raised regarding myopathy, which may lead to fatal rhabdomyolysis. This review examines current evidence on statin interactions, mechanism of injury and toxicity.
Significant myopathy is rare with an incidence of less than 0.5% of patients. Statin side effects may be dose-related, associated with other drug interactions that interfere with statin metabolic pathways through cytochrome p450 pathways or glucuronidation, or related to co-morbidities. Several theories have suggested that statin myotoxicity may be due to intracellular cholesterol depletion, or interference with oxidative phosphorylation pathways. Exact mechanisms are yet to be fully defined. Individuals with mixed dyslipidaemia may require combination therapy to achieve target lipid levels. No large-scale randomized trials have yet reported on the safety of combination therapy, although more recent studies may shed some light when they report.
As most individuals on statins are 'high-risk' patients, they tend to be on multiple agents for cardiovascular disease which may interact with their statin. Progression of myalgia or myositis to rhabdomyolysis is rare (one in 30-100,000 patient-years of exposure), but if progressive muscle symptoms are ignored then fatalities can occur. When prescribing statins, physicians should be alert to potential risks and educate patients to report any potentially significant symptoms.
他汀类药物已被公认为心血管疾病降胆固醇的一线药物,越来越多的证据支持起始使用他汀类药物,且指南推荐进行治疗以降低低密度脂蛋白水平。尽管他汀类药物一般耐受性良好,副作用较少,包括头痛和胃肠道症状,但人们对其可能导致致命性横纹肌溶解的肌病表示担忧。本综述探讨了关于他汀类药物相互作用、损伤机制和毒性的现有证据。
严重肌病很少见,发生率低于患者的0.5%。他汀类药物的副作用可能与剂量相关,与通过细胞色素P450途径或葡萄糖醛酸化干扰他汀类药物代谢途径的其他药物相互作用有关,或与合并症有关。有几种理论认为,他汀类药物的肌毒性可能是由于细胞内胆固醇耗竭或对氧化磷酸化途径的干扰。确切机制尚未完全明确。混合性血脂异常患者可能需要联合治疗以达到目标血脂水平。尽管更多近期研究报告时可能会有所启示,但尚无大规模随机试验报道联合治疗的安全性。
由于大多数服用他汀类药物的个体是“高危”患者,他们往往同时服用多种治疗心血管疾病的药物,这些药物可能与他汀类药物发生相互作用。肌痛或肌炎进展为横纹肌溶解很少见(每30 - 100,000患者年暴露中有1例),但如果忽视进行性肌肉症状,则可能发生死亡。开具他汀类药物时,医生应警惕潜在风险,并教育患者报告任何可能有意义的症状。