Symptomatic intracranial hemorrhage in the ALIAS Multicenter Trial: relationship to endovascular thrombolytic therapy

BackgroundIn the ALIAS (Albumin in Acute Stroke) Part 2 Multicenter Trial, 85% of subjects received standard-of-care intravenous tissue plasminogen activator, and 21% received some form of endovascular thrombolysis. The overall rate of symptomatic intracranial hemorrhage was within the expected range but was higher in albumin-treated subjects than in saline-treated subjects. Aims and MethodsUsing the trial's Public Use Dataset, we analyzed factors contributing to symptomatic and asymptomatic intracranial hemorrhage in the safety sample' of 830 subjects. ResultsFour hundred sixteen subjects received albumin therapy, and 414 received saline. Intravenous tissue plasminogen activator was given to 682%; intravenous tissue plasminogen activator plus endovascular intervention in 164%; and endovascular therapy alone in 43%. Symptomatic intracranial hemorrhage occurred in 41 subjects - within the first 12h in one-third of cases, and within the first day in approximate to 60%. Intravenous tissue plasminogen activator had been used in 78% of symptomatic intracranial hemorrhage subjects - no higher than in the overall cohort. In contrast, 488% of subjects with symptomatic intracranial hemorrhage had received endovascular therapy - a rate markedly higher than the 207% rate for the entire cohort (P=00001). Sixty-eight point three percent of subjects with symptomatic intracranial hemorrhage had received albumin, and 317% saline (risk ratio 214, P=0025). Other factors associated with symptomatic intracranial hemorrhage were baseline NIHSS and ASPECTS scores and the SEDAN score. Forty-one point four percent of subjects with symptomatic intracranial hemorrhage died. The odds ratio for symptomatic intracranial hemorrhage was 389 (95% confidence interval 204-741) with endovascular therapy and 215 (confidence interval 108-425) with albumin. ConclusionsEndovascular thrombolysis was the major factor predisposing to symptomatic intracranial hemorrhage, and albumin contributed to this predisposition. The latter may be mediated by albumin's influence on platelet aggregation or collateral perfusion.