Newman Connie B, Palmer Gary, Silbershatz Halit, Szarek Michael
Pfizer Global Pharmaceuticals, 235 East 42nd Street, New York, NY 10017-5755, USA.
Am J Cardiol. 2003 Sep 15;92(6):670-6. doi: 10.1016/s0002-9149(03)00820-8.
This analysis assessed the safety of atorvastatin in the 10- to 80-mg dose range using pooled data from 44 completed trials comprising 16,495 dyslipidemic patients treated with atorvastatin (n = 9,416), placebo (n = 1,789), and other statins (n = 5,290). A retrospective analysis was conducted and included treatment-associated adverse events, serious adverse events, and musculoskeletal and hepatic adverse events. Only 3% (n = 241) of atorvastatin-treated patients withdrew from studies due to treatment-associated adverse events, compared with 1% of those (n = 16) on placebo and 4% of those (n = 188) receiving other statins; the most frequently reported treatment-associated adverse events were related to the digestive system. Serious adverse events were rare and seldom led to withdrawal. Persistent elevations in hepatic transaminases to >3 times the upper limit of normal (ULN) were experienced by 0.5% (n = 47) of atorvastatin-treated patients. A persistent elevation in creatine phosphokinase (CPK) (>10 x ULN) was observed in only 1 atorvastatin-treated patient and was not associated with myopathy. The incidence of treatment-associated myalgia was low in the atorvastatin (1.9% [n = 181]), placebo (0.8% [n = 14]), and other statin (2.0% [n = 105]) groups, and was not related to the atorvastatin dose. No cases of rhabdomyolysis or myopathy were reported. Thus, the overall incidence of treatment-associated adverse events observed with atorvastatin did not increase in the 10- to 80-mg dose range, and was similar to that observed with placebo and in patients treated with other statins. Specific analysis of musculoskeletal and hepatic adverse events showed that these occurred infrequently and rarely resulted in treatment discontinuation.
本分析使用来自44项已完成试验的汇总数据，评估了10至80毫克剂量范围阿托伐他汀的安全性，这些试验包括16495名接受阿托伐他汀治疗的血脂异常患者（n = 9416）、安慰剂治疗患者（n = 1789）以及其他他汀类药物治疗患者（n = 5290）。进行了一项回顾性分析，包括与治疗相关的不良事件、严重不良事件以及肌肉骨骼和肝脏不良事件。在接受阿托伐他汀治疗的患者中，仅有3%（n = 241）因与治疗相关的不良事件退出研究，相比之下，接受安慰剂治疗的患者中有1%（n = 16）退出，接受其他他汀类药物治疗的患者中有4%（n = 188）退出；最常报告的与治疗相关的不良事件与消化系统有关。严重不良事件罕见，很少导致停药。0.5%（n = 47）接受阿托伐他汀治疗的患者出现肝转氨酶持续升高至正常上限（ULN）的3倍以上。仅在1例接受阿托伐他汀治疗的患者中观察到肌酸磷酸激酶（CPK）持续升高（>10×ULN），且与肌病无关。阿托伐他汀组、安慰剂组和其他他汀类药物组中与治疗相关的肌痛发生率较低，分别为1.9%（n = 181）、0.8%（n = 14）和2.0%（n = 105），且与阿托伐他汀剂量无关。未报告横纹肌溶解或肌病病例。因此，在10至80毫克剂量范围内，阿托伐他汀治疗相关不良事件的总体发生率未增加，与安慰剂组以及接受其他他汀类药物治疗的患者相似。对肌肉骨骼和肝脏不良事件的具体分析表明，这些不良事件很少发生，很少导致治疗中断。
