Alsheikh-Ali Alawi A, Ambrose Marietta S, Kuvin Jeffrey T, Karas Richard H
Molecular Cardiology Research Institute, Department of Medicine, Tufts-New England Medical Center, 750 Washington St, Boston, MA 02111, USA.
Circulation. 2005 Jun 14;111(23):3051-7. doi: 10.1161/CIRCULATIONAHA.105.555482. Epub 2005 May 23.
Statins are currently the mainstay of dyslipidemia management for the primary and secondary prevention of cardiovascular disease. Controversial concerns about the safety of the newly marketed statin rosuvastatin have been raised on the basis of premarketing studies and a few postmarketing reports.
We reviewed rosuvastatin-associated adverse events reported to the US Food and Drug Administration over its first year of marketing. On the basis of prescription data obtained from IMS Health, rates of adverse event reports (AERs) per million prescriptions were calculated. Rates of rosuvastatin-associated AERs over its first year of marketing were compared with those seen with atorvastatin, simvastatin, and pravastatin over the concurrent timeframe and during their respective first years of marketing. Comparison was also made to the first year of marketing of cerivastatin. The primary analysis examined the composite end point of AERs of rhabdomyolysis, proteinuria, nephropathy, or renal failure. With either timeframe comparison, rosuvastatin was significantly more likely to be associated with the composite end point of rhabdomyolysis, proteinuria, nephropathy, or renal failure AERs. Reported cases of rhabdomyolysis, proteinuria, or renal failure tended to occur early after the initiation of therapy and at relatively modest doses of rosuvastatin. The increased rate of rosuvastatin-associated AERs relative to other widely used statins was also observed in secondary analyses when other categories of AERs were examined, including adverse events with serious outcomes, liver toxicity, and muscle toxicity without rhabdomyolysis.
The present analysis supports concerns about the relative safety of rosuvastatin at the range of doses used in common clinical practice in the general population.
他汀类药物目前是血脂异常管理中用于心血管疾病一级和二级预防的主要药物。基于上市前研究和一些上市后报告，人们对新上市的他汀类药物瑞舒伐他汀的安全性提出了有争议的担忧。
我们回顾了瑞舒伐他汀上市第一年向美国食品药品监督管理局报告的相关不良事件。根据从艾美仕市场研究公司获得的处方数据，计算每百万张处方的不良事件报告率。将瑞舒伐他汀上市第一年的相关不良事件报告率与阿托伐他汀、辛伐他汀和普伐他汀在同一时间段及其各自上市第一年的报告率进行比较。还与西立伐他汀上市第一年进行了比较。主要分析考察了横纹肌溶解、蛋白尿、肾病或肾衰竭不良事件的复合终点。无论采用哪种时间框架比较，瑞舒伐他汀与横纹肌溶解、蛋白尿、肾病或肾衰竭不良事件复合终点的关联显著更常见。报告的横纹肌溶解、蛋白尿或肾衰竭病例往往在治疗开始后早期出现，且瑞舒伐他汀剂量相对适中。在对其他不良事件类别进行检查的二次分析中，包括有严重后果的不良事件、肝毒性和无横纹肌溶解的肌肉毒性，也观察到瑞舒伐他汀相关不良事件报告率相对于其他广泛使用的他汀类药物有所增加。
本分析支持了对普通人群临床实践中常用剂量范围内瑞舒伐他汀相对安全性的担忧。
