Treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm with tranexamic acid: a double-blind clinical trial. Antifibrinolytic treatment in subarachnoid hemorrhage. Antifibrinolysis with tranexamic acid in aneurysmal subarachnoid hemorrhage: a consecutive controlled clinical trial. The use of antifibrinolytic agents in the preoperative treatment of ruptured intracranial aneurysms. Effect of tranexamic acid on rebleeding after subarachnoid hemorrhage: a double-blind controlled clinical trial. Antifibrinolytic treatment in subarachnoid hemorrhage: a randomized placebo-controlled trial. STAR Study Group. Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms. A double-blind placebo-controlled study. Tranexamic acid in subarachnoid hemorrhage. A double-blind study.
A double-blind clinical trial of tranexamic acid was carried out on 39 patients with fresh subarachnoid hemorrhage from a ruptured aneurysm. Twenty patients received tranexamic acid, 6 gm daily for 14 to 21 days, while 19 patients received conventional therapy of bedrest and dexamethasone when cerebral edema developed, plus isotonic saline. Rebleeding and mortality were reduced by one-fourth and one-fifth, respectively (p less than 0.001). No side-effects were observed. Tranexamic acid is valuable in the treatment of subarachnoid hemorrhage caused by ruptured intracranial aneurysms. We enrolled 479 patients with subarachnoid hemorrhage in a multicenter, randomized, double-blind, placebo-controlled trial to determine whether treatment with the antifibrinolytic agent tranexamic acid improves outcome by preventing rebleeding. At three months there was no statistical difference between the outcomes in the tranexamic acid group and the control group. Of the 173 patients who died, 84 had received tranexamic acid and 89 placebo (95 per cent confidence interval for the difference in mortality rate, -6 to 11 per cent). Similarly, when analysis was restricted to patients with an angiographically demonstrated aneurysm, there was no significant difference between the groups. This absence of effect was not due to a lack of antifibrinolytic action, since the rate of rebleeding was reduced from 24 per cent in the control group to 9 per cent in the tranexamic acid-treated group (chi-square = 18.07, P less than 0.001), but resulted from a concurrent increase in the incidence of ischemic complications (15 per cent in the control group and 24 per cent in the tranexamic acid group; chi-square = 8.07, P less than 0.01). We conclude that until some method can be found to minimize ischemic complications, tranexamic acid is of no benefit in patients with subarachnoid hemorrhage. A randomized controlled clinical trial was carried out to study the effect of tranexamic acid (AMCA, Cyklokapron; AB Kabi, Stockholm, Sweden) in the prevention of early rebleeding after the rupture of an intracranial aneurysm. The incidence of vasospasm, hydrocephalus, cerebral ischemic and thromboembolic complications, morbidity, and mortality was also evaluated. The series comprises 59 patients, 30 treated with tranexamic acid and 29 controls. The treatment was stopped if there was rebleeding, operation, or discharge from the hospital. There were 6 recurrent hemorrhages in 6 patients in the tranexamic acid-treated group and 11 recurrences in 7 patients in the control group. Recurrent hemorrhages occurred later in tranexamic acid-treated patients than in controls. Five patients in each group died from rebleeding. Five additional treated patients and 2 controls died from cerebral ischemic dysfunction. The results suggest that tranexamic acid may protect patients with ruptured aneurysms from rebleeding for 1 or 2 weeks, but that it also may produce cerebral ischemic complications. nan In a double-blind controlled clinical trial on 51 patients with subarachnoid hemorrhage, tranexamic acid, 4 gm per day for ten consecutive days, did not favorably affect the outcome. Neither mortality nor rebleeding rates were improved after a follow-up of three months. To investigate whether antifibrinolytics in combination with treatment to prevent cerebral ischemia improve outcome in patients with subarachnoid hemorrhage (SAH) in whom occlusion of the aneurysm is delayed.
                Antifibrinolytic treatment reduces rebleeding, but outcome does not improve because of a concurrent increase in the occurrence of cerebral ischemia. Because treatment of ischemia has improved, antifibrinolytics might now have a beneficial effect.
                A prospective, double-blind, placebo-controlled multicenter clinical trial was performed. Randomized were 462 patients (229 received tranexamic acid, 233 placebo) admitted within 96 hours after onset of SAH, in whom treatment of the aneurysm was delayed beyond 48 hours after SAH. All patients were treated with calcium antagonists and hypervolemia. At 3 months, outcome was assessed with the Glasgow Outcome Scale. The occurrence of cerebral ischemia and other complications were recorded, and the effects of treatment were related to the clinical condition on admission.
                Antifibrinolytic treatment had no beneficial effect on outcome (relative risk [RR], 1.10; 95% confidence limits [CL], 0.91-1.34). Antifibrinolytics significantly reduced the occurrence of rebleeding (RR, 0.58; 95% CL, 0.42-0.80); the occurrence of ischemic and other complications was the same in the two groups.
                Antifibrinolytic treatment combined with treatment to prevent cerebral ischemia does not improve outcome. One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind, placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid (TXA) in the management of ruptured intracranial aneurysms. The incidence of recurrent haemorrhage between active and placebo groups was identical (12%) and the mortality from recurrent haemorrhage was 7% and 5%, respectively. The overall incidence of cerebral infarction before surgery, at discharge and at 6 months follow-up was greater in the TXA group (27%) than in the control group (11%). Post-operative cerebral ischaemia was significantly more frequent in the active, 18 of 29 as compared to 6 of 32 patients, in the placebo group. In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow (CBF) on the side of the ruptured aneurysm in the TXA treated group. It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group. There was no significant difference in the incidence of cerebral vasospasm, hydrocephalus, visual disturbances and gastrointestinal disturbances. More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5% level. Given that disability was due to either vasospasm or recurrent haemorrhage than a patient under TXA treatment was significantly more likely to have disability due to vasospasm (p less than 0.04); the reverse was true for the placebo patient (p less than 0.05). The effects of intravenous tranexamic acid were compared with placebo in 64 patients with subarachnoid hemorrhage. A double-blind procedure was used. One gram of tranexamic acid was given intravenously every 4 hours up to the time of operation on an intracranial arterial aneurysm or for up to 21 days after the first bleeding if operative treatment was not feasible. There were no differences in re-bleeds, morbidity or mortality between the tranexamic and placebo-treated groups. No thromboembolic complications were noted in either group. Our results do not support the use of tranexamic acid in subarachnoid hemorrhage in daily doses of 6 g.
Treatment does not improve clinical outcome because the benefit is offset by an increase in poor outcome caused by cerebral ischaemia as a result of treatment with antifibrinolytics. These data do not support the routine use of antifibrinolytic drugs in the treatment of patients with aneurysmal subarachnoid haemorrhage.