Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage

  • Review
  • Intervention




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.


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.



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。




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。


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。




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)。





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



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.