Streptokinase in Acute Ischemic Stroke: An Individual Patient Data Meta-Analysis

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Abstract
Background and Purpose —Three major randomized controlled trials of streptokinase in acute ischemic stroke were curtailed because of safety concerns. The prospective Thrombolysis in Acute Stroke Pooling Project (TAS-PP) was established to examine the aggregate data to identify factors influencing the effect of streptokinase. Methods —Individual patient data from the Australian Streptokinase Trial (ASK), Multicentre Acute Stroke Trial-Europe (MAST-E), Multicentre Acute Stroke Trial-Italy (MAST-I), and Glasgow Trial (Glasgow) were pooled. Multivariate modeling determined the interaction between treatment effect and delay from symptom onset to treatment, predicted baseline risk, age, concomitant aspirin or heparin use, and the presence of early CT signs on the outcomes of 10-day death, death and disability, or death alone at 3 or 6 months. Results —Patients’ records were pooled (total 1292 patients; streptokinase, n=653, no streptokinase n=639). The subgroup analysis of treatment effect according to delay from symptoms to inclusion shows only a trend toward a better treatment effect with shorter delay, which is not statistically significant for any outcome. Heavier patients in MAST-E may have had a lower (non significant) risk from the fixed dose of 1.5 million units of streptokinase. Concomitant aspirin increased the excess mortality rates in streptokinase-treated patients (17% without aspirin versus 91% with aspirin, P =0.005). The presence of early CT scan signs did not increase the detrimental effect of streptokinase. Conclusions —Few factors influenced the response to streptokinase. However, earlier administration, lower doses of streptokinase, and avoidance of concomitant aspirin should be considered if further streptokinase trials in acute stroke are planned.