Clinical and pharmacological aspects of thrombolytic therapy for ischemic stroke

Rational. Thrombolytic therapy is an effective method of treating ischemic stroke, which has its limitations associated with the peculiarities of introducing a recombinant plasminogen activator (International non-proprietary name Alteplase); from 2020, it is possible to use an alternative thrombolytic drug “Recombinant protein containing the staphylokinase amino acid sequence” of Russian production.

Aims. To evaluate the clinical efficacy and safety profile of the domestic thrombolytic drug non-immunogenic staphylokinase in patients with acute ischemic stroke and to justify the possibilities of personalized therapy based on clinical and pharmacological predictors of outcome.

Materials and methods. A retrospective analysis of 576 patients with ischemic stroke who received systemic thrombolytic therapy with the drug produced in Russia–non-immunogenic staphylokinase was carried out. The dynamics of neurological deficits according to the National Institutes of Health Stroke Scale (NIHSS) at 24 hours, functional status according to the modified Rankin scale at 90 days, hospital and 90-day mortality, hemorrhagic transformation of the ischemia focus and intracerebral hemorrhages, including symptomatic ones, were evaluated. Additionally, a stratified analysis of out-comes by age, body weight, and comorbidity was performed, and a machine learning model (CatBoostClassifier) was constructed to predict death by calculating the area under the ROC-curve.

Results. The average age of patients was 68.2 ± 12.7 years, the proportion of women was 49.0 %. Hospital mortality was 11 %. Symptomatic hemorrhagic transformation of the ischemic focus was observed in 5.5 % of cases. Patients who died in hospital were characterized by greater baseline neurological deficits, greater functional dependence, older age, more frequent heart failure, abnormal heart rhythms, and cardioembolic stroke subtype. A prognostic model based on clinical laboratory features showed a ROC-AUC of 0.89 (95% confidence interval 0.82–0.95) when predicting fatal outcome.

Conclusions. Systemic thrombolysis with non-immunogenic staphylokinase in patients with ischemic stroke was associated with acceptable safety, a low incidence of clinically significant hemorrhagic complications, and reproducible predictors of fatal outcome. The data obtained indicate the possibility of risk stratification and clinical and pharmacological justification of personalized thrombolytic therapy in conditions of limited availability of imported drugs.

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