Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial
Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial
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DOI：
10.1016/s1474-4422(14)70084-5
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发表时间：
2014-07-01
期刊：
影响因子：
48
通讯作者：
Collaborators, S. T. A. S. H.
中科院分区：
文献类型：
--
作者：
Kirkpatrick, Peter J.;Turner, Carole L.;Collaborators, S. T. A. S. H.
背景他汀类药物对急性蛛网膜下腔出血患者的益处尚不清楚。我们的目的是确定是否辛伐他汀40毫克可以改善这种disorder.Methods的患者的长期结局，在这个国际，多中心，随机，双盲试验，我们招募了患者年龄在18-65岁的证实证据的蛛网膜下腔出血，并提出不到96小时的发作从35个急性神经外科中心在9个国家。患者被随机分配（1：1）接受辛伐他汀40 mg或安慰剂，每天一次，最多21天。我们使用计算机生成的随机化代码，经常将每个中心的患者随机分组（5名辛伐他汀，5名安慰剂）。参与者和研究者对治疗分配设盲。主要结局是6个月时通过问卷获得的改良兰金量表（mRS）评分的分布。对意向治疗人群进行分析。这项试验已经完成，并在当前对照试验中注册，编号为ISRCTN 75948817。结果在2007年1月6日至2013年2月1日期间，除了2009年5月15日至2011年2月8日期间暂停招募外，803例患者被随机分配接受辛伐他汀40 mg（n=391）或安慰剂（n=412）。所有患者均纳入意向治疗人群。782例（97%）患者在6个月时记录了结局数据，其中560例（72%）被归类为具有良好结局，mRS 0-2（辛伐他汀组271例患者vs安慰剂组289例患者）。根据年龄和入院时世界神经外科医生联合会分级调整的mRS主要顺序分析得出的常见比值比（OR）为0.97，95% CI 0.75-1.25; p=0.803。在6个月时，我们记录了辛伐他汀组37例（10%）死亡，而安慰剂组35例（9%）死亡（对数秩p=0.592）。辛伐他汀组报告了70例（18%）严重不良事件，而安慰剂组为74例（18%）。STASH试验未发现辛伐他汀对蛛网膜下腔出血患者的长期或短期结局有任何益处。尽管证明没有安全性问题，我们得出结论，蛛网膜下腔出血患者不应该在急性期常规治疗辛伐他汀。
Background The benefit of statins in patients with acute aneurysmal subarachnoid haemorrhage is unclear. We aimed to determine whether simvastatin 40 mg could improve the long-term outcome in patients with this disorder.Methods In this international, multicentre, randomised, double-blind trial, we enrolled patients aged 18-65 years with confirmatory evidence of an aneurysmal subarachnoid haemorrhage and presenting less than 96 h from ictus from 35 acute neurosurgical centres in nine countries. Patients were randomly allocated (1:1) to receive either simvastatin 40 mg or placebo once a day for up to 21 days. We used a computer-generated randomisation code to randomise patients in every centre by blocks often (five simvastatin, five placebo). Participants and investigators were masked to treatment assignment. The primary outcome was the distribution of modified Rankin Scale (mRS) score obtained by questionnaire at 6 months. Analyses were done on the intention-to-treat population. This trial has been completed and is registered with Current Controlled Trials, number ISRCTN75948817.Findings Between Jan 6, 2007, and Feb 1, 2013, apart from the period between May 15, 2009, and Feb 8, 2011, when recruitment was on hold, 803 patients were randomly assigned to receive either simvastatin 40 mg (n=391) or placebo (n=412). All patients were included in the intention-to-treat population. 782 (97%) patients had outcome data recorded at 6 months, of whom 560 (72%) were classed as having a favourable outcome, mRS 0-2 (271 patients in the simvastatin group vs 289 in the placebo group). The primary ordinal analysis of the mRS, adjusted for age and World Federation of Neurological Surgeons grade on admission, gave a common odds ratio (OR) of 0.97, 95% CI 0.75-1.25; p=0.803. At 6 months, we recorded 37 (10%) deaths in the simvastatin group compared with 35 (9%) in the placebo group (log-rank p=0.592). 70 (18%) serious adverse events were reported in the simvastatin group compared with 74 (18%) in the placebo group. No suspected unexpected serious adverse reactions were reported.Interpretation The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage. Despite demonstrating no safety concerns, we conclude that patients with subarachnoid haemorrhage should not be treated routinely with simvastatin during the acute stages.