Anticoagulants for acute ischaemic stroke

 

Abstract

Background

Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulants might improve outcome if bleeding risks were low. This is an update of a Cochrane review first published in 1995, and previously updated in 2004.

Objectives

To assess the effect of anticoagulant therapy versus control in the early treatment (less than 14 days) of patients with acute ischaemic stroke.

Search methods

We searched the Cochrane Stroke Group Trials Register (last searched 2 October 2007), and two Internet clinical trials registries for relevant ongoing studies (last searched October 2007).

Selection criteria

Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke.

Data collection and analysis

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

Main results

Twenty-four trials involving 23,748 participants were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on 11 trials (22,776 participants) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio (OR) 1.05; 95% confidence interval (CI) 0.98 to 1.12) at the end of follow up. Similarly, based on eight trials (22,125 participants), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow up (OR 0.99; 95% CI 0.93 to 1.04). Although anticoagulant therapy was associated with fewer recurrent ischaemic strokes (OR 0.76; 95% CI 0.65 to 0.88), it was also associated with an increase in symptomatic intracranial haemorrhages (OR 2.55; 95% CI 1.95 to 3.33). Similarly, anticoagulants reduced the frequency of pulmonary emboli (OR 0.60; 95% CI 0.44 to 0.81), but this benefit was offset by an increase in extracranial haemorrhages (OR 2.99; 95% CI 2.24 to 3.99).

Authors' conclusions

Since the last version of the review, neither of the two new relevant studies have provided additional information to change the conclusions. In patients with acute ischaemic stroke, immediate anticoagulant therapy is not associated with net short or long-term benefit. Treatment with anticoagulants reduced recurrent stroke, deep vein thrombosis and pulmonary embolism, but increased bleeding risk. The data do not support the routine use of any the currently available anticoagulants in acute ischaemic stroke.

 

Plain language summary

Anticoagulants for acute ischaemic stroke

Millions of people around the world have strokes every year. Most strokes take place when a blood clot blocks a blood vessel leading to the brain. Without a proper blood supply, the brain quickly suffers damage, which can be permanent. The damage from a stroke can cause arm or leg weakness, or difficulties with language or vision. Strokes are sometimes fatal, but will more often leave the survivor unable to do the things that they used to do. Because strokes are common and cause such damage, researchers are trying to find ways to get rid of the blood clot soon after the stroke happens. One way to do this is with blood thinning drugs called anticoagulants. If anticoagulants work, the bad effects of the stroke might be avoided. The main problem with anticoagulants is that they can cause bleeding, which can sometimes be very serious. This systematic review was designed to find out whether people treated with anticoagulants early after stroke got better or not, and whether they had problems with bleeding. There is a lot of information in this systematic review - 23,748 people with stroke have been involved in 24 included randomised trials to answer this question. People treated with anticoagulants had less chance of developing blood clots in their legs and in their lungs following their stroke, but these benefits were offset by an increased risk of bleeding. More research is needed to find out if there are ways to select the people with stroke who will benefit from anticoagulants without suffering the bleeding complications. This review did not provide any evidence that the early use of anticoagulants is of overall benefit to people with strokes caused by blood clots. Anticoagulants did not reduce disability, and caused more bleeding.

 

摘要

背景

急性缺血性中風的抗凝血藥物治療

大部分缺血性中風的成因來自於腦部的動脈遭血栓阻斷所致。若患者出血風險較低，則可採用抗凝血藥物預防血栓形成以改善預後。這項結論第一次發表於1995年,而考科藍資料庫於2004年曾更新，目前再次更新

目標

本文獻回顧之目的是評估在急性缺血性中風患者，早期使用抗凝血藥物治療相對於控制組而言的效用為何。

搜尋策略

我們搜尋了Cochrane中風組試驗登錄(上次搜尋是西元2007年10月2日)以及為了搜尋相關正在進行的研究,也找了兩個網際網路臨床資料庫(上次搜尋是西元2007年10月)。

選擇標準

針對急性缺血性中風的疑似或確定患者於早期(中風發生的兩週內開始)使用抗凝血藥物治療相對於控制組作隨機試驗比較。

資料收集與分析

2名文獻回顧作者根據納入條件分別選擇臨床試驗，評估試驗品質並擷取資料。

主要結論

有24個臨床試驗共23,748位患者被選入。各臨床試驗的品質相差頗大。受測試的抗凝血藥物包括有傳統肝素(standard unfractionated heparin), 低分子量肝素(lowmolecularweight heparins),類肝素(heparinoids), 口服抗凝血藥物(oral anticoagulants), 及血栓抑制劑(thrombin inhibitors)。依據其中11個臨床試驗(共22,776個患者)，最後追蹤結果發現，沒有證據顯示抗凝血藥物治療會降低全死亡原因的比率(OR 1.05;95%信賴區間:0.98 – 1.12)。類似的結果也出現在另8個臨床試驗(共22,125患者)，最後追蹤結果發現，沒有證據顯示抗凝血藥物會降低死亡或殘障的比率(OR 0.99;95%信賴區間:0.93 – 1.04)。雖然使用抗凝血藥物治療與少數減少再次發生缺血性中風的案例相關(OR = 0.76;95%信賴區間0.65 – 0.88)，然而卻也增加有症狀的顱內出血中風的案例(OR = 2.55;95%信賴區間:1.95 – 3.33)。相似的研究亦發現,能減少肺栓塞案例(OR = 0.60;95%信賴區間:0.44 – 0.81)，但是這好處卻因會額外增加重大顱外出血而被抵銷(OR 2.99; 95% CI 2.24 to 3.99)。

作者結論

就最新的文獻回顧來看，兩個新的相關研究皆未提供足以改變這項結論的額外資訊。對於急性缺血性中風的患者，立即投予抗凝血藥物的治療，不管就短期或長期皆沒有益處。抗凝血藥物的治療可用在降低再次中風，減少深部靜脈栓塞及肺栓塞的機會，但會增加出血的危險性。本回顧性文獻的資料並不支持常規使用任何種類的抗凝血藥物來治療急性缺血性中風患者。

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

每年全世界有百萬人發生中風，大部分中風原因為血塊堵塞腦部的血管，一旦缺乏應有的血流，腦部將很快發生損傷，且將持續永久，來自於中風的損傷可能造成手腳無力,無法言語或視覺障礙。中風有時是有致命性，但大部分可順利存活，不過無法再做之前經常做的事。由於中風相當常見且危害甚深，因此研究學者試著找出中風後盡快解除血栓的問題。其中一個解決方法即是抗凝血劑。一旦抗凝血劑發生功用，中風引起的不良效應也許可以避免。抗凝血劑的主要問題是其可能引發出血，此問題也時須嚴肅看待。本篇系統性文獻回顧之目的為找出早期給予抗凝血劑後之中風病人是否發生較佳或其他效應，及是否發生出血等問題。在這個系統性回顧當中有大量資訊—其包含23,748位中風病人及24個隨機研究，來回答這個問題. 以抗凝血劑來治療的病人較少在中風後發生腳部或肺部血栓。但這些受益與出血危險度增加互相抵銷。大部分的研究試圖找出方法來挑選中風病人，使其能自抗凝血劑受益，而不受出血併發症的影響。此篇文獻無法提供證據證明中風病人早期接受抗凝血劑治療，有整體利益存在。抗凝血劑無法減少失能的發生，但可能增加出血的機會。