Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
Int J Cardiol. 2014 Jun 1;174(1):83-9. doi: 10.1016/j.ijcard.2014.03.150. Epub 2014 Mar 28.
Two randomised controlled trials have found a higher risk of rhabdomyolysis in users of 80 mg versus 20 mg simvastatin, but there is very limited information about the risk associated with other doses. We undertook a nested case-control study, using routinely collected national health and drug dispensing data, to estimate the relative and absolute risks of rhabdomyolysis resulting in hospital admission or death according to simvastatin dose.
The underlying study cohort comprised all patients (n=313,552) who initiated a new episode of simvastatin use in New Zealand between 1 May 2005 and 31 December 2009. Cases (n=29) were patients with a diagnosis of rhabdomyolysis after cohort entry, confirmed by hospital discharge letter or death records. Ten controls, matched by year of birth and sex, were randomly selected from the study cohort using risk set sampling. Current users of 40 mg simvastatin daily were about five times as likely to develop rhabdomyolysis as those taking 20mg; the adjusted odds ratio was 5.3 (95% CI 1.9-15.0). The absolute excess risk of rhabdomyolysis associated with the use of 40 mg versus 20mg was about 10 per 100,000 person-years; the crude incidence rates were 11.5 (95% CI 7.1-17.5) and 2.1 (95% CI 0.7-4.8) per 100,000 person-years respectively.
These findings provide reassurance that the absolute risk of rhabdomyolysis in a general population of simvastatin users is very low. Nonetheless, they also raise questions about the optimal simvastatin regimen to maximise cardiovascular benefits and minimise the risk of serious muscle injury.
两项随机对照试验发现，80 毫克辛伐他汀的使用者横纹肌溶解的风险高于 20 毫克，但关于其他剂量相关风险的信息非常有限。我们进行了一项嵌套病例对照研究，使用常规收集的国家卫生和药物配药数据，根据辛伐他汀剂量估计导致住院或死亡的横纹肌溶解的相对风险和绝对风险。
基础研究队列包括所有于 2005 年 5 月 1 日至 2009 年 12 月 31 日期间在新西兰开始使用新的辛伐他汀疗程的患者（n=313552）。病例（n=29）是队列入组后诊断为横纹肌溶解的患者，通过医院出院记录或死亡记录确认。使用风险集抽样法，从研究队列中随机选择 10 名年龄和性别相匹配的对照者。每天服用 40 毫克辛伐他汀的患者发生横纹肌溶解的可能性是服用 20 毫克的五倍；调整后的优势比为 5.3（95%CI 1.9-15.0）。与使用 40 毫克相比，使用 40 毫克与使用 20 毫克的横纹肌溶解绝对风险增加约 10/100,000 人年；粗发病率分别为 11.5（95%CI 7.1-17.5）和 2.1（95%CI 0.7-4.8）/100,000 人年。
这些发现表明，一般辛伐他汀使用者发生横纹肌溶解的绝对风险非常低。尽管如此，它们也提出了关于最佳辛伐他汀方案的问题，以最大限度地提高心血管益处并最小化严重肌肉损伤的风险。
