Drugs to prevent clots after bleeding in the brain

Review question

What is the effectiveness and safety of medications used to prevent clots (antithrombotic treatments) both in the early stages and long-term in people who have had a bleed within their brain (intracerebral haemorrhage)?

Background

People with stroke due to bleeding in the brain (also known as intracerebral haemorrhage: ICH) are more likely to develop clots in their blood vessels due to immobility (in the early stages) and due to other medical conditions (in the long term). Blood clots in the lungs, brain, or other organs can cause serious illness or death. Drugs that prevent clots (also known as 'antithrombotic drugs') might be useful to stop clot formation in people with ICH. However, these drugs can also cause serious bleeding complications.

Study characteristics

From extensive searches conducted on 8 March 2017, we identified two relevant randomised controlled trials (RCTs), which are the fairest tests of treatment. There were 121 participants in these two trials, which compared blood-thinning 'anticoagulant' drugs (heparin in one and enoxaparin in the other) delivered by injections under the skin versus no anticoagulant drug soon after ICH.

Key results

The primary outcome of this review was the combined risk of several important clinical outcome events (such as another intracerebral haemorrhage, ischaemic stroke, or death from a cardiovascular cause). We were not able to calculate this outcome for the included studies. Neither RCT reported on recovery of independence or mental abilities. One RCT involving 46 participants reported on case fatality associated with short-term antithrombotic treatment, and did not find a statistically meaningful effect. For the consequences of treatment that could be analysed, the risk estimates were imprecise and uncertain. Therefore, the potential benefits and harms of antithrombotic drugs soon after a stroke due to bleeding in the brain remain unclear. New high-quality RCTs investigating the use of antithrombotic treatment after stroke due to ICH appear justified and are needed.

Quality of the evidence

The overall quality of the evidence was low. This is due to the way the included trials were conducted and reported, as well as the small number of participants, which may not have been high enough to detect small differences between the antithrombotic treatment and no antithrombotic treatment groups.

Authors' conclusions: 

There is insufficient evidence from RCTs to support or discourage the use of antithrombotic treatment after ICH. RCTs comparing starting versus avoiding antiplatelet or anticoagulant drugs after ICH appear justified and are needed in clinical practice.

Read the full abstract...
Background: 

Survivors of stroke due to intracerebral haemorrhage (ICH) are at risk of thromboembolism. Antithrombotic (antiplatelet or anticoagulant) treatments may lower the risk of thromboembolism after ICH, but they may increase the risks of bleeding.

Objectives: 

To determine the overall effectiveness and safety of antithrombotic drugs for people with ICH.

Search strategy: 

We searched the Cochrane Stroke Group Trials Register (24 March 2017). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL: the Cochrane Library 2017, Issue 3), MEDLINE Ovid (from 1948 to March 2017), Embase Ovid (from 1980 to March 2017), and online registries of clinical trials (8 March 2017). We also screened the reference lists of included trials for additional, potentially relevant studies.

Selection criteria: 

We selected all randomised controlled trials (RCTs) of any antithrombotic treatment after ICH.

Data collection and analysis: 

Three review authors independently extracted data. We converted categorical estimates of effect to the risk ratio (RR) or odds ratio (OR), as appropriate. We divided our analyses into short- and long-term treatment, and used fixed-effect modelling for meta-analyses. Three review authors independently assessed the included RCTs for risks of bias and we created a 'Summary of findings' table using GRADE.

Main results: 

We included two RCTs with a total of 121 participants. Both RCTs were of short-term parenteral anticoagulation early after ICH: one tested heparin and the other enoxaparin. The risk of bias in the included RCTs was generally unclear or low, with the exception of blinding of participants and personnel, which was not done. The included RCTs did not report our chosen primary outcome (a composite outcome of all serious vascular events including ischaemic stroke, myocardial infarction, other major ischaemic event, ICH, major extracerebral haemorrhage, and vascular death). Parenteral anticoagulation did not cause a statistically significant difference in case fatality (RR 1.25, 95% confidence interval (CI) 0.38 to 4.07 in one RCT involving 46 participants, low-quality evidence), ICH, or major extracerebral haemorrhage (no detected events in one RCT involving 75 participants, low-quality evidence), growth of ICH (RR 1.64, 95% CI 0.51 to 5.29 in two RCTs involving 121 participants, low-quality evidence), deep vein thrombosis (RR 0.99, 95% CI 0.49 to 1.96 in two RCTs involving 121 participants, low quality evidence), or major ischaemic events (RR 0.54, 95% CI 0.23 to 1.28 in two RCTs involving 121 participants, low quality evidence).

Share/Save