Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage

  • Review
  • Intervention

Authors


Abstract

Background

Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably due to dissolution of the clot by natural fibrinolytic activity.

Objectives

To assess the effect of antifibrinolytic treatment in patients with aneurysmal subarachnoid haemorrhage.

Search methods

We searched the Cochrane Stroke Group Trials Register, the Cochrane Controlled Trials Register, MEDLINE and EMBASE (last searched June 2002) and reference lists of articles. We also contacted drug companies.

Selection criteria

Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid or an equivalent) with control in people with confirmed subarachnoid haemorrhage.

Data collection and analysis

Two reviewers independently selected trials for inclusion and extracted the data. All five reviewers assessed trial quality.

Main results

Nine trials involving 1399 patients were included. Based on 1041 patients in three trials, antifibrinolytic treatment did not show any evidence of benefit for poor outcome (death, vegetative state or severe disability) with an odds ratio of 1.12, 95% confidence interval 0.88 to 1.43. Death from all causes was not significantly influenced by treatment across all nine trials (odds ratio 0.99, 95% confidence interval 0.79 to 1.24). Antifibrinolytic treatment reduced the risk of re-bleeding reported at the end of follow-up, with some heterogeneity between the trials (odds ratio 0.55, 95% confidence interval 0.42 to 0.71). Treatment increased the risk of cerebral ischaemia in five trials (odds ratio 1.39, 95% confidence interval 1.07 to 1.82) with considerable heterogeneity between the most recent study (Roos 2000), in which specific treatments to prevent cerebral ischaemia were used, and the four older studies. Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus in five trials (odds ratio 1.14, 95% confidence interval 0.86 to 1.51).

Authors' conclusions

Treatment does not improve clinical outcome because the benefit is offset by an increase in poor outcome caused by cerebral ischaemia as a result of treatment with antifibrinolytics. These data do not support the routine use of antifibrinolytic drugs in the treatment of patients with aneurysmal subarachnoid haemorrhage.

摘要

背景

抑制纖維蛋白溶解之治療 (antifibrinolytic therapy),於動脈瘤破裂性蜘蛛膜下腔出血 (aneurysmal subarachnoid haemorrhage) 的使用

再出血是動脈瘤破裂性蜘蛛膜下腔出血的病人死亡及失能的重要原因。再出血可能是因為體內自然的纖維蛋白溶解之活動 (natural fibrinolytic activity) 而導致血塊崩解。

目標

這篇回顧論文的目標是評估於動脈瘤破裂性蜘蛛膜下腔出血的病人,使用抑制纖維蛋白溶解之治療的效果。

搜尋策略

我們搜尋了Cochrane Stroke Group Trials Register、the Cochrane Controlled Trials Register、Medline、Embase (2002年6月最後一次搜尋)、以及文獻當中的參考目錄。我們也和製藥公司取得聯繫。

選擇標準

於確定蜘蛛膜下腔出血的病人中,比較口服或經靜脈給予抑制纖維蛋白溶解之藥物 (tranexamic acid, epsilon aminocaproic acid或相等物) 與對照組的隨機試驗。

資料收集與分析

2位回顧作者獨立地選擇納入的試驗並擷取數據。5位回顧作者評估試驗品質。

主要結論

我們收錄了包涵1399位病人的9個試驗。根據3個試驗中1041位病人的結果,抑制纖維蛋白溶解之治療並無法顯示對於不良預後 (死亡、植物人狀態、或嚴重失能) 有益的證據 (odds ratio of 1.12, 95% confidence interval 0.88 to 1.43)。在所有9個試驗當中,治療對於所有原因造成的死亡並沒有顯著的影響(odds ratio 0.99,95% confidence interval 0.79 to 1.24)。在後續追蹤結束時,抑制纖維蛋白溶解之治療有顯示能降低再出血的危險性,但在不同試驗之間存在著一些不一致性 (odds ratio 0.55,95% confidence interval 0.42 to 0.71)。在個5試驗當中,治療增加腦缺血的危險性 (odds ratio 1.39,95% confidence interval 1.07 to 1.82),但最近的1個試驗 (Ross 2000,於試驗中有採用專一性的治療以預防腦缺血) 與先前的4個試驗之間,存在著相當多的不一致性。在個5試驗當中,抑制纖維蛋白溶解之治療對於水腦 (hydrocephlus) 發生的比例並沒有顯示治療的效果 (odds ratio 1.14,95% confidence interval 0.86 to 1.51)。

作者結論

因為抑制纖維蛋白溶解之藥物治療的益處,由於導致腦缺血而造成不良臨床結果的增加而抵銷,所以治療並無法改善臨床結果。這些數據並不支持於動脈瘤破裂性蜘蛛膜下腔出血之病人的治療中常規地使用抑制纖維蛋白溶解的藥物。

翻譯人

本摘要由奇美醫院張偉倫翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

預防血塊崩解的治療並無法改善蜘蛛膜下腔出血後的臨床結果。蜘蛛膜下腔出血是在所謂的蜘蛛膜下腔當中發生流血的情形,那是界於腦部與顱骨之間一個非常狹小的空間,在其中包含著供應腦部血流的血管。出血的原因通常是在這些血管中有一個脆弱的點破裂造成的。這個脆弱的點像一個小汽球或者是水泡,它被稱為動脈瘤。蜘蛛膜下腔出血是一種相對上不常見的中風類型;它大約占了所有中風的百分之5。不同於其他常見的中風類型,蜘蛛膜下腔出血發生的年齡通常相對上較為年輕:一半的病人年齡小於60歲。發生蜘蛛膜下腔出血的病人其臨床結果一般而言是不良的:一半的病人於出血後的第1個月內死亡,存活超過一個月的病人當中,有一半的人日常生活活動仍然依賴旁人的協助(例如:步行、穿衣服、洗澡)。蜘蛛膜下腔出血後造成不良臨床結果的最重要原因之一是發生所謂再出血的合併症。再出血被認為是源於破裂動脈瘤所在之處的血塊崩解而造成的。這種崩解可能是由於蜘蛛膜下腔出血後,於蜘蛛膜下腔中自然的纖維蛋白溶解之活動所造成的。既然抑制纖維蛋白溶解的物質能降低這種活動,抑制纖維蛋白溶解之治療可以被建議為,蜘蛛膜下腔出血後減少再出血的發生並因此減少不良臨床結果的方法。這篇回顧論文顯示抑制纖維蛋白溶解之治療的確降低再出血的危險性。但令人驚訝地,在存活以及日常生活活動能獨立的臨床結果上,並沒有因為抑制纖維蛋白溶解之治療而有所改善。這篇回顧論文的進一步分析顯示:降低再出血危險性的益處事實上被其他合併症的增加而抵銷。因為抑制纖維蛋白溶解之治療對於臨床結果並沒有整體上有益的療效,所以回顧作者之總結為:抑制纖維蛋白溶解之藥物不應使用於動脈瘤破裂性蜘蛛膜下腔出血病人的治療中。

Plain language summary

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage

Treatment to prevent blood-clot dissolution does not improve outcome after subarachnoid haemorrhage. A subarachnoid haemorrhage (SAH) is a bleed in the so-called subarachnoid space, which is the very small space between the brain and the skull, and which contains blood vessels that supply the brain. The cause of the bleeding usually is a rupture of a weak spot in one of these vessels. This weak spot is like a small balloon, or blister, which is called an aneurysm. A subarachnoid haemorrhage is a relatively uncommon type of stroke; it accounts for about 1 in 20 (5%) of all strokes. In contrast to common types of stroke, a subarachnoid haemorrhage often occurs at a relatively young age: half the patients are younger than 60 years. The outcome of patients after subarachnoid haemorrhage is generally poor: half the patients die within one month after the haemorrhage, and of those who survive the first month, half remain dependent for help with activities of daily living (e.g.: walking, dressing, bathing). One of the most important causes of poor outcome after SAH is the occurrence of a complication called rebleeding. Rebleeding is thought to originate from dissolution of the blood-clot at the site of the ruptured aneurysm. This dissolution probably results from natural fibrinolytic activity in the subarachnoid space after SAH. Since antifibrinolytic agents reduce this activity, antifibrinolytic therapy was suggested as a means of reducing the occurrence of rebleeds and therefore to result in a decrease of poor outcome after SAH. The review demonstrates that antifibrinolytic treatment does indeed reduce the risk of rebleeding. Surprisingly, clinical outcome - in terms of survival and being independent in activities of daily living - does not improve by antifibrinolytic treatment. Further analysis in the review shows that the beneficial effect of a reduced risk of rebleeding is in fact nullified by an increase in one of the other complications. Because there is no overall beneficial effect of antifibrinolytic treatment on outcome the reviewers conclude that antifibrinolytic drugs should not be used in the treatment of patients with aneurysmal SAH.

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