Antiplatelet therapy for aneurysmal subarachnoid haemorrhage

A subarachnoid haemorrhage (SAH) is a type of stroke due to bleeding in the subarachnoid space, which is the small space between the brain and the skull, and which contains blood vessels that supply the brain. The cause of the bleeding is usually a rupture of a bulge in one of these vessels, which is called an aneurysm. The outcome of patients after SAH is generally poor: 50% of patients die within one month after the haemorrhage, and of those who survive the initial month, 50% remain dependent on someone else for help with activities of daily living (eg, walking, dressing, bathing). One of the causes of poor outcome is a complication of SAH called secondary ischaemia (ischaemia means lack of blood). This complication occurs four to 10 days after the haemorrhage (hence secondary). The cause is not exactly known, but besides contraction of the blood vessels in the brain, there is evidence that clotting of blood platelets plays a role as well. Therefore, trials have been performed with agents that prevent clotting of blood platelets (antiplatelet agents). In this review of seven trials, including 1385 patients, that studied the effects of antiplatelet agents on the outcome after SAH, we found that patients who were treated with antiplatelet agents had a poor outcome less often, and secondary ischaemia less often than patients that received no antiplatelet agent, but the results were not statistically significant and so no definite conclusion can be drawn. Moreover, patients who are treated with antiplatelet agents might have a slightly higher risk of bleeding. Based on these results we conclude that antiplatelet agents after SAH cannot be recommended at the present time.

Authors' conclusions: 

This review shows a trend towards better outcome in patients treated with antiplatelet agents, possibly due to a reduction in secondary ischaemia. However, results were not statistically significant, thus no definite conclusions can be drawn. Also, antiplatelet agents could increase the risk of haemorrhagic complications. On the basis of the current evidence treatment with antiplatelet agents in order to prevent secondary ischaemia or poor outcome cannot be recommended.

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Background: 

Secondary ischaemia is a frequent cause of poor outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). Besides vasospasm, platelet aggregation seems to play a role in the pathogenesis of secondary ischaemia. Experimental studies have suggested that antiplatelet agents can prevent secondary ischaemia.

Objectives: 

To determine whether antiplatelet agents change outcome in patients with aneurysmal SAH.

Search strategy: 

We searched the Cochrane Stroke Group Trials Register (last searched August 2006), MEDLINE (1966 to August 2006) and EMBASE databases (1980 to August 2006). We also searched reference lists of identified trials.

Selection criteria: 

All randomised controlled trials (RCTs) comparing any antiplatelet agent with control in patients with aneurysmal SAH.

Data collection and analysis: 

Two review authors independently extracted the data and assessed trial quality. Relative risks (RR) were calculated with regard to poor outcome, case fatality, secondary ischaemia, haemorrhagic intracranial complications and aneurysmal rebleeding according to the intention-to-treat principle. In case of a statistically significant primary analysis, a worst case analysis was performed.

Main results: 

Seven RCTs were included in the review, totalling 1385 patients. Four of these trials met the criteria for good quality studies. For any antiplatelet agent there were reductions of a poor outcome (RR 0.79, 95% confidence interval (CI) 0.62 to 1.01) and secondary brain ischaemia (RR 0.79, 95% CI 0.56 to 1.22) and more intracranial haemorrhagic complications (RR 1.36, 95% CI 0.59 to 3.12), but none of these differences were statistically significant. There was no effect on case fatality (RR 1.01, 95% CI 0.74 to 1.37) or aneurysmal rebleeding (RR 0.98, 95% CI 0.78 to 1.38). For individual antiplatelet agents, only ticlopidine was associated with statistically significant fewer occurrences of a poor outcome (RR 0.37, 95% CI 95% CI 0.14 to 0.98) but this estimate was based on only one small RCT.

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