Antiplatelet Therapy in Aneurysmal Subarachnoid Hemorrhage
Graeme J. Hankey MD, FRCP Section Editor:
Secondary ischemia is a frequent cause of poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). Besides vasospasm, platelet aggregation seems to play a role in the pathogenesis of secondary ischemia. Experimental studies have suggested that antiplatelet agents can prevent secondary ischemia. The objective of this review was 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 randomized 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) with corresponding 95% confidence intervals (CIs) were calculated with regard to poor outcome, case fatality, secondary ischemia, hemorrhagic 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, totaling 1385 patients. Four of these trials met predefined criteria for good quality studies. For any antiplatelet agent there were reductions of poor outcome (RR 0.79, 95% CI 0.62 to 1.01; Figure) and secondary brain ischemia (RR 0.79, 95% CI 0.56 to 1.22) and more intracranial hemorrhagic 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 toward better outcome in patients treated with antiplatelet agents, possibly because of a reduction in secondary ischemia. However, results were not statistically significant, thus no definite conclusions can be drawn. Also, antiplatelet agents could increase the risk of hemorrhagic complications. On the basis of the current evidence, treatment with antiplatelet agents to prevent secondary ischemia or poor outcome cannot be recommended.
Before antiplatelet drugs could be recommended in clinical practice, appropriately powered RCTs are needed. However, it is difficult to make recommendations as to which antiplatelet agent is the most promising agent, as there were no large differences between the antiplatelet drugs. Only ticlopidine showed a statistically significant result, but this drug is not commonly used anymore because of hematologic complications. As there was only one RCT that included patients whose aneurysms were treated by endovascular coiling, it could be worthwhile to perform a new pilot study in patients whose aneurysm are treated by coiling.1
- Received November 2, 2007.
- Accepted November 21, 2007.