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与其他他汀类药物相比,辛伐他汀是否会导致更多的肌毒性?

Does simvastatin cause more myotoxicity compared with other statins?

机构信息

Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City, KS 66160, USA.

出版信息

Ann Pharmacother. 2009 Dec;43(12):2012-20. doi: 10.1345/aph.1M410. Epub 2009 Nov 17.

Abstract

OBJECTIVE

To review the literature regarding statins and myotoxicity and evaluate these data to determine whether incidence rates are higher with simvastatin.

DATA SOURCES

Literature was identified from a search of MEDLINE (1966-August 2009) and International Pharmaceutical Abstracts (1970-August 2009), as well as references of selected articles. Key search terms included the names of individual statins, rhabdomyolysis, myopathy, myalgia, myotoxicity, statins, and drug interactions.

STUDY SELECTION AND DATA EXTRACTION

All English-language articles discussing statin-related myotoxicity and relevant drug interactions that involved human subjects were examined.

DATA SYNTHESIS

Simvastatin is a commonly prescribed, moderately potent statin. Recent evidence suggests that the risk of severe muscle toxicity with simvastatin may be higher than that with other statins, particularly when used in combination with cytochrome P450 isoenzyme inhibitors. However, the lack of direct comparative clinical trials assessing the risk of myotoxicity among the statins in equivalent doses precludes definitive conclusions. Data sources examining low-to-moderate doses of simvastatin suggest that myotoxicity with this agent is infrequent, with rates similar to those seen with other statins. Conversely, findings from clinical trials using the maximum daily dose (80 mg) and a clinical trials database of varying doses of simvastatin suggest a possible increase in rates of myotoxicity with the 80-mg dose compared with lower doses and a higher incidence rate when compared with maximum doses of other statins.

CONCLUSIONS

Overall, the rates of severe myotoxicity with all statins are low, especially with low-to-moderate doses. However, recent trials for those using simvastatin 80 mg daily suggest a higher incidence of myotoxicity compared with maximum approved doses of other statins. Practitioners should be aware of these possible risks and individualize therapy to limit myotoxicity.

摘要

目的

回顾他汀类药物与肌毒性相关的文献,并评估这些数据,以确定辛伐他汀的发生率是否更高。

资料来源

通过对 MEDLINE(1966 年-2009 年 8 月)和国际药学文摘(1970 年-2009 年 8 月)进行检索,以及对选定文章的参考文献进行检索,确定了文献。关键检索词包括各种他汀类药物的名称、横纹肌溶解症、肌病、肌痛、肌毒性、他汀类药物和药物相互作用。

研究选择和数据提取

所有讨论他汀类药物相关肌毒性和涉及人体的相关药物相互作用的英文文章均进行了检查。

数据综合

辛伐他汀是一种常用的、中等强度的他汀类药物。最近的证据表明,辛伐他汀发生严重肌肉毒性的风险可能高于其他他汀类药物,尤其是与细胞色素 P450 同工酶抑制剂合用时。然而,由于缺乏在等效剂量下评估他汀类药物肌毒性风险的直接比较临床试验,因此无法得出明确的结论。检查辛伐他汀低至中等剂量的资料来源表明,该药物发生肌毒性的情况并不常见,其发生率与其他他汀类药物相似。相反,使用最大日剂量(80mg)的临床试验和辛伐他汀不同剂量的临床试验数据库的研究结果表明,与较低剂量相比,80mg 剂量时肌毒性的发生率可能增加,与其他他汀类药物的最大剂量相比,肌毒性的发生率更高。

结论

总的来说,所有他汀类药物严重肌毒性的发生率均较低,尤其是在低至中等剂量时。然而,最近针对辛伐他汀每日 80mg 的试验表明,与其他他汀类药物的最大批准剂量相比,肌毒性的发生率更高。临床医生应意识到这些可能的风险,并个体化治疗以限制肌毒性。

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