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长效他汀治疗颅内动脉瘤性蛛网膜下腔出血:一项随机、双盲、安慰剂对照试验。

Long-acting statin for aneurysmal subarachnoid hemorrhage: A randomized, double-blind, placebo-controlled trial.

机构信息

1 Department of Neurosurgery, Hirosaki University School of Medicine & Hospital, Hirosaki, Japan.

2 Department of Neurosurgery, Towada City Hospital, Towada, Japan.

出版信息

J Cereb Blood Flow Metab. 2018 Jul;38(7):1190-1198. doi: 10.1177/0271678X17724682. Epub 2017 Aug 1.

Abstract

Statins have pleiotropic effects that are considered beneficial in preventing cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (aSAH). Many studies using statins have been performed but failed to show remarkable effects. We hypothesized that a long-acting statin would be more effective, due to a longer half-life and stronger pleiotropic effects. Patients with aSAH were randomly assigned to a pitavastatin group (4 mg daily; n = 54) and a placebo group ( n = 54) after repair of a ruptured aneurysm. The primary efficacy end point was vasospasm-related delayed ischemic neurological deficits (DIND), and the secondary end points were cerebral vasospasm evaluated by digital subtraction angiography (DSA), vasospasm-related new cerebral infarctions, and outcome at three months. Severe cerebral vasospasms on DSA were statistically fewer in the pitavastatin group than in the placebo group (14.8% vs. 33.3%; odds ratio, 0.32; 95% confidence interval, 0.11-0.87, p = 0.042); however, the occurrence of DIND and new infarctions and outcome showed no statistically significant differences between the groups. The present study is the first to prove the definite, statin-induced amelioration of cerebral vasospasm on DSA. However, administration of any type of statin at the acute phase of aSAH is not recommended.

摘要

他汀类药物具有多种有益作用,被认为可预防蛛网膜下腔出血(aSAH)后脑血管痉挛和迟发性脑缺血。许多使用他汀类药物的研究都已经进行,但未能显示出显著的效果。我们假设长效他汀类药物会更有效,因为半衰期更长,具有更强的多效性作用。在修复破裂的动脉瘤后,将 aSAH 患者随机分配到匹伐他汀组(每天 4mg;n=54)和安慰剂组(n=54)。主要疗效终点是血管痉挛相关的迟发性缺血性神经功能缺损(DIND),次要终点是数字减影血管造影(DSA)评估的血管痉挛、血管痉挛相关的新脑梗死和三个月时的结局。DSA 上的严重血管痉挛在匹伐他汀组明显少于安慰剂组(14.8% vs. 33.3%;比值比,0.32;95%置信区间,0.11-0.87,p=0.042);然而,DIND 和新梗死的发生以及结局在两组之间没有统计学上的显著差异。本研究首次证明了他汀类药物可明确改善 DSA 上的血管痉挛。然而,不建议在 aSAH 的急性期使用任何类型的他汀类药物。

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