Antiplatelet therapy for aneurysmal subarachnoid haemorrhage

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Abstract
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. To determine whether antiplatelet agents change outcome in patients with aneurysmal SAH. 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. All randomised controlled trials (RCTs) comparing any antiplatelet agent with control in patients with aneurysmal SAH. 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. 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. 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.