Negative Interaction of Aspirin and Streptokinase in Acute Ischemic Stroke: Further Analysis of the Multicenter Acute Stroke Trial-Italy

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Abstract
Background: Thrombolytic therapy improves the functional outcome in acute ischemic stroke, but the risk of death and cerebral hemorrhage remains high. Aspirin given together with a thrombolytic agent may worsen the risk-to-benefit ratio. We performed a further Multicenter Acute Stroke Trial-Italy (MAST-I) which is the only randomized, controlled trial that has tested the effect of this combination to evaluate the risk of aspirin use plus streptokinase. Patients and Methods: We made a post hoc analysis of the MAST-I results comparing streptokinase plus aspirin (156 patients) with streptokinase alone (157 patients). We evaluated the risk of death and cerebral hemorrhage. Results: The combined regimen significantly increased early case fatality from day 3–10 (53 vs. 30; OR 2.1; CI 1.2–3.6). The death excess was solely due to treatments and was not explained by the main prognostic predictors (multifactorial analysis). The cause of death in the combination group was mainly cerebral (42 vs. 24; OR 2.0; CI 1.3–3.7) and associated with hemorrhagic transformation (22 vs. 11; OR 2.2; CI 1.0–5.0). The rate of stroke reoccurrence was not increased in patients treated with streptokinase alone (15 vs. 11; OR 1.4; CI 0.6–3.4). Conclusions: Stroke patients treated with streptokinase plus aspirin have an increased risk of early death, probably due to cerebral hemorrhagic complications. Whenever thrombolytics are chosen for acute stroke treatment, aspirin and other antiplatelet agents should be avoided.