Anticoagulants for preventing recurrence following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack

 

Abstract

Background

After a first ischaemic stroke, further vascular events due to thromboembolism are common and often fatal. Anticoagulants could potentially reduce the risk of such events, but any benefits could be offset by an increased risk of fatal or disabling haemorrhages.

Objectives

To assess the effect of prolonged anticoagulant therapy compared with placebo or open control following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack.

Search methods

We searched the Cochrane Stroke Group Trials Register in May 2008. In June 2008 we searched three online trial registers, used Web of Science Cited Reference Search to identify new citations of previously included studies, contacted a pharmaceutical company, and also contacted authors for additional information on included trials.

Selection criteria

Randomised and quasi-randomised trials comparing at least one month of anticoagulant therapy with control in people with previous, presumed non-cardioembolic, ischaemic stroke or transient ischaemic attack.

Data collection and analysis

Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data.

Main results

Eleven trials involving 2487 participants were included. The quality of the nine trials which predated routine computerised tomography (CT) scanning and the use of the International Normalised Ratio to monitor anticoagulation was poor. There was no evidence of an effect of anticoagulant therapy on either the odds of death or dependency (two trials, odds ratio (OR) 0.83, 95% confidence interval (CI) 0.52 to 1.34) or of 'non-fatal stroke, myocardial infarction, or vascular death' (four trials, OR 0.96, 95% CI 0.68 to 1.37). Death from any cause (OR 0.95, 95% CI 0.73 to 1.24) and death from vascular causes (OR 0.86, 95% CI 0.66 to 1.13) were not significantly different between treatment and control. The inclusion of two recently completed trials did not alter these conclusions. There was no evidence of an effect of anticoagulant therapy on the risk of recurrent ischaemic stroke (OR 0.85, 95% CI 0.66 to 1.09). However, anticoagulants increased fatal intracranial haemorrhage (OR 2.54, 95% CI 1.19 to 5.45), and major extracranial haemorrhage (OR 3.43, 95% CI 1.94 to 6.08). This is equivalent to anticoagulant therapy causing about 11 additional fatal intracranial haemorrhages and 25 additional major extracranial haemorrhages per year for every 1000 patients given anticoagulant therapy.

Authors' conclusions

Compared with control, there was no evidence of benefit from long-term anticoagulant therapy in people with presumed non-cardioembolic ischaemic stroke or transient ischaemic attack, but there was a significant bleeding risk.

 

Plain language summary

Anticoagulants for preventing recurrence following presumed non-cardioembolic ischaemic stroke or transient ischaemic attack

Most strokes are due to a sudden blockage of an artery in the brain (this type of stroke is called an ischaemic stroke). In most ischaemic strokes, the blockage is caused by a blood clot. In patients with an irregular heart rhythm (atrial fibrillation), anticoagulant drugs, such as warfarin, prevent such clots forming and prevent stroke. However, anticoagulant drugs may also cause bleeding in the brain and this harmful effect could outweigh any benefits in patients with a normal heart rhythm. This review identified 11 trials, involving 2487 participants who had had a stroke (and also had a normal heart rhythm), of anticoagulants to prevent further strokes. There was good evidence that anticoagulants could cause serious bleeding, and there was no evidence that, in such patients, anticoagulants were of benefit in the prevention of further strokes. Other trials have shown that, in a person with a normal heart rhythm who has had an ischaemic stroke, antiplatelet drugs such as aspirin are a safe and effective way to reduce the risk of further strokes and heart attacks.

 

摘要

背景

抗凝血劑在非心臟病引起的腦栓塞或非心臟病引起的暫時性腦缺血的病人,預防中風的效果

在第一次中風後,之後因血栓性栓塞而造成的血管性事件,特別是心肌梗塞和再次中風,都是常見且通常致命的. 抗凝血劑有可能降低這些血管性事件,但他的好處會因增加致死性或失能性出血而抵銷

目標

這篇文獻回顧的目的在於評估在非心臟病引起的腦栓塞或非心臟病引起的暫時性腦缺血的病人,長期使用抗凝血劑治療(和以安慰劑或其他藥物治療為對照)的效果.

搜尋策略

我們搜尋了Cochrane Stroke Group trials register.我們也聯絡了抗凝血劑的廠商. 本回顧最近期的研究是2002年8月發表的.

選擇標準

在非心臟病引起的腦栓塞或非心臟病引起的暫時性腦缺血的病人,至少使用抗凝血劑治療1個月,且有對照組的隨機分配和quasirandomised trials.

資料收集與分析

2個回顧者獨立選擇試驗並評估試驗品質和節錄數據

主要結論

11個包含2487人的試驗被收錄. 有9個試驗,因為是在電腦斷層檢查還沒被常規使用前即發表和使用INR來監控的品質不好,所以品質是差的. 抗凝血劑治療對於死亡率或殘障率降低,在2個試驗是無效的(odds ratio 0.83, 95% confidence interval [CI] 0.52 to 1.34);而對於非致死性中風,心肌梗塞或血管性死亡,在4個試驗中顯示無效(odds ratio 0.96, 95% CI 0.68 – 1.37). 全死亡率(odds ratio 0.95, 95% CI 0.73 to 1.24)和血管性疾病致死(odds ratio 0.86, 95% CI 0.66 to 1.13),兩組也無統計學上差異.2個最新完成的試驗的結果也相同. 抗凝血劑治療對於預防再次梗塞性中風並無效果(odds ratio 0.85, 95% CI 0.66 to 1.09). 但是,抗凝血劑增加了致死性顱內出血(odds ratio 2.54, 95% CI 1.19 to 5.45),及重大的顱外出血(odds ratio 3.43, 95% CI 1.94 to 6.08). 這相當於每1000人接受抗凝血劑治療,每年有11人發生致死性顱內出血,有25人發生重大的顱外出血.

作者結論

跟對照組相比,在非心臟病引起的腦栓塞或非心臟病引起的暫時性腦缺血的病人,使用長期抗凝血劑治療並無證據顯示有好處,但卻有顯著的出血危險.

翻譯人

本摘要由奇美醫院何乘彰翻譯。

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

總結

大部分中風者是因為腦動脈的急性阻塞,此類型稱之為缺血性中風. 在大多數的缺血性中風,是由血塊導致阻塞的. 在不規則心律,像是心房顫動的病人,抗凝血劑像是warfarin能阻止血栓形成所以能預防中風. 但是,也能導致腦出血,因此用於正常心律者必須權衡利弊. 這篇回顧選擇了11個試驗,共2487個曾經中風過的正常心律者來使用抗凝血劑去預防中風. 其中,有相當好的證據顯示抗凝血劑會導致嚴重出血且沒有任何證據支持這些病人服用抗凝血劑能預防再中風. 有些試驗顯示那些曾經中風過但正常心律的病人使用抗血小板藥物像是aspirin是一種安全且有效的方式去降低再中風及心臟病發生.