Randomized Study Of Ticlopidine On Cerebral Vasospasm Following Ruptured Aneurysm

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Abstract
Based on our hypothesis for the mechanisms of chronic cerebral vasospasm following subarachnoid hemorrhage (SAH), we have made a randomized study of Ticlopidine in preventing cerebral vasospasm in 71 patients with ruptured aneurysm. In a double blind cross-over set up-S. 200 mg T.I.D. vs. placebo - the induction of circulating platelet aggregates by venous occlusion was highly significantly inhibited. Materials and Methods: Ticlopidine is a potent inhibitor of platelet aggregation and adhesiveness. The inhibitory nature of this drug is distinct from that of Aspirin which not only is an inhibitor of platelet aggregation butalso suppresses PGI2 generation in the vascular wall. Fourty one patients were given Ticlopidine (400 mg/day) and 30 patients served as a control group. All patients underwent direct intracranial operation and 46 of them were operated upon 4 days after SAH. High density which indicates subarachnoid clot was observed on pre- and postoperative CT scans in the majority of both groups. Results: Mortality was 12% in Ticlopidine group and 17% in control group. As for morbidity, excellent results were obtained 57% in Ticlopidine group and 42% in control group in Grade 1-3. In order to know the effects of Ticlopidine on cerebral vasospasm and ischemic neurological deficit caused by vasospasm, 32 patients who did not show preoperative neurological deficit and underwent surgery within 4 days after SAH were analized in relation to the presence or absence of high density on postoperative CT. The development of postoperative vasospasm was almost same (71.4-76.5%) in two groups, but permanent ischemic neurological deficit was 28.6% in Ticlopidine group and 66.7% in control group when postoperative CT scan showed high density in subarachnoid space. This preliminary randomized study indicates that Ticlopidine may be effective on prevention of postoperative ischemic neurological deficits due to vasospasm.

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