Abstract
Based on preclinical studies suggesting that recombinant tissue plasminogen activator (rt-PA) may promote ischemic brain injuries, we investigated in patients the possible risk of worse clinical outcome after rt-PA treatment as a result of its inability to resolve cerebral ischemia. Here, we designed a cohort study using a retrospective analysis of patients who received treatment with intravenous (4.5-h window) or intraarterial rt-PA, without or with thrombectomy. Controls were consecutive patients who did not receive recanalization treatment, who met all inclusion criteria. As a marker of reperfusion, we defined the variable of early neurological improvement as the difference between the score of the National Institute of Health Stroke Scale (NIHSS) (at admission and 24 h). The main variable was worsening of the patient’s functional situation in the first 3 months. To compare quantitative variables, we used Student’s t test or the Mann-Whitney test. To estimate the odds ratios of each independent variable in the patient’s worsening in the first 3 months, we used a logistic regression model. We included 1154 patients; 577 received rt-PA, and 577 served as controls. In the group of patients treated with rt-PA, 39.4% who did not present clinical reperfusion data developed worsening within 3 months after stroke compared with 3.5% of patients with reperfusion (P < 0.0001). These differences were not significant in the control group. In summary, administration of rt-PA intravenously or intraarterially without reperfusion within the first 24 h may be associated with a higher risk of functional deterioration in the first 3 months.
Highlights
Stroke is the second leading cause of death in developed countries, the second leading cause of dementia, and the leading cause of major disability in adults, with an increasing incidence because of the progressive aging of the population in such countries
Our hypothesis was based on two possible scenarios: (1) If the thrombolytic activity of recombinant tissue plasminogen activator (rt-PA) is effective and cerebral ischemia rapidly resolved, the blood-brain barrier remains intact with the rt-PA maintained within the vascular compartment, leading to a better clinical outcome; (2) if the rt-PA cannot play its thrombolytic action leading to a prolonged cerebral ischemia, rt-PA could enhance damages of the blood-brain barrier and of the cerebral parenchyma, leading to a worse clinical outcome [17]
1154 patients were included in this study, 577 of whom received rt-PA (387 intravenous, 93 intraarterial, and 97 intravenous plus intraarterial with or without thrombectomy), and 577 controls
Summary
Stroke is the second leading cause of death in developed countries, the second leading cause of dementia, and the leading cause of major disability in adults, with an increasing incidence because of the progressive aging of the population in such countries. The clinical evidence on the neurotoxicity associated with rt-PA treatment following ischemic stroke is still debated, and it is of crucial importance to reduce risks after administration of the thrombolytic agent for a better patient management [15, 16]. Our hypothesis was based on two possible scenarios: (1) If the thrombolytic activity of rt-PA is effective and cerebral ischemia rapidly resolved, the blood-brain barrier remains intact with the rt-PA maintained within the vascular compartment, leading to a better clinical outcome; (2) if the rt-PA cannot play its thrombolytic action leading to a prolonged cerebral ischemia, rt-PA could enhance damages of the blood-brain barrier and of the cerebral parenchyma, leading to a worse clinical outcome [17]
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