Predicting the safety of intravenous thrombolysis with Fortelyzin in patients over 60 years of age with ischemic stroke using the THRIVE scale

   Objective: to evaluate the prognostic value of the THRIVE scale in patients aged 60 years and older with ischemic stroke (IS) after intravenous thrombolysis with Fortelyzin® (INN/chemical name – recombinant protein containing the amino acid sequence of staphylokinase; SuperGene LLC, Russia) compared to alteplase, based on a retrospective analysis of the results of the FRIDA randomised clinical trial.

   Material and methods. Patients (n = 336) were randomly assigned to either the Fortelyzin group (n = 168) or the alteplase group (n = 168). There were 124 patients (74 %) aged 60 years or older in the Fortelyzin group and 123 patients (73 %) in the alteplase group, and these patients were included in the analysis presented. Patients aged 60 years and older were also divided into two groups according to their modified Rankin scale (mRS) score on day 90: a group with a good functional outcome (mRS 0–2) and a group with an unfavourable functional outcome (mRS 3–6). The THRIVE scale was used to predict outcomes after treatment with Fortelyzin or alteplase. AUC values were then calculated. AUC ROC values were compared using the DeLong criterion.

   Results. For all-cause mortality at day 90, the predicted AUC value on the THRIVE scale was 0.8 (0.71–0.9) in the Fortelyzin group and 0.76 (0.66–0.87) in the alteplase group (p = 0.57). For adverse functional outcomes, the AUC value was 0.73 (0.64–0.82) in the Fortelyzin group and 0.79 (0.71–0.87) in the alteplase group (p = 0.36).

   Conclusion. The study confirmed the high predictive value of the THRIVE scale for predicting mortality and adverse outcomes in patients aged 60 years and older with IS after treatment with Fortelyzin and alteplase.

1. Feigin VL, Brainin M, Norrving B, et al. World Stroke Organization (WSO): global stroke fact sheet. Int J Stroke. 2022;17(1):18-29. doi: 10.1177/17474930211065917

2. Saposnik G, Cote R, Phillips S, et al; Stroke Outcome Research Canada (SORCan) Working Group. Stroke outcome in those over 80: a multicenter cohort study across Canada. Stroke. 2008;39(8):2310-7. doi: 10.1161/STROKEAHA.107.511402

3. Kastrup A, Brunner F, Hildebrandt H, et al. THRIVE score predicts clinical and radiological outcome after endovascular therapy or thrombolysis in patients with anterior circulation stroke in everyday clinical practice. Eur J Neurol. 2017;24(8):1032-9. doi: 10.1111/ene.13328

4. Flint AC, Cullen SP, Faigeles BS, Rao VA. Predicting long-term outcome after endovascular stroke treatment: the totaled health risks in vascular events score. Am J Neuroradiol. 2010;31(7):1192-6. doi: 10.3174/ajnr.A2050

5. Collen D. Staphylokinase: a potent, uniquely fibrin-selective thrombolytic agent. Nature Med. 1998;4:279-84. doi: 10.1038/nm0398-279

6. Christener RB, Boyle MD. Role of Staphylokinase in the acquisition of plasmin-(ogen) dependent enzymatic activity by Staphylococci. J Infect Dis. 1986;173:104-12. doi: 10.1093/infdis/173.1.104

7. Verstraete M. Third-Generation Thrombolytic Drugs. Am J Med. 2000;109:52-8. doi: 10.1016/s0002-9343(00)00380-6

8. Markin SS, Ivanov SV, Beletsky IP, et al. Assessment of the allergenic and immunotoxic properties of the recombinant non-immunogenic staphylokinase in preclinical and clinical trials. Pharmacy & Pharmacology. 2025;13(1):31-44 (In Russ.). doi: 10.19163/2307-9266-2025-13-1-31-44

9. Ivanov SV, Beletsky IP, Zakharova MV, et al. Study of the pharmacokinetics of non-immunogenic staphylokinase in patients with acute myocardial infarction and acute ischemic stroke. Pharmacy & Pharmacology. 2025;13(5):415-28 (In Russ.). doi: 10.19163/2307-9266-2025-13-5-415-428

10. Gusev EI, Martynov MYu, Nikonov AA, et al. Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4.5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial. Lancet Neurology. 2021;20:721-8. doi: 10.1016/S1474-4422(21)00210-6

11. Shamalov NA, Martynov MYu, Yarovaya EB, et al. Thrombolysis with the non-immunogenic staphylokinase for acute ischaemic stroke in FORPI registry: an observational study. Stroke. 2026;57(2):394-403. doi: 10.1161/STROKEAHA.125.051115

12. Wnuk M, Drabik L, Derbisz J, Slowik A. Prognostic significance of age in patients with acute ischaemic stroke treated with intravenous thrombolysis. Neurologia i Neurochirurgia Polska. 2022;56(1):81-8. doi: 10.5603/PJNNS.a2022.0010

13. Yaghi S, Willey JZ, Cucchiara B, et al. Treatment and outcome of hemorrhagic transformation after intravenous alteplase in acute ischemic stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017;48(12):343-61. doi: 10.1161/STR.0000000000000152

14. Flint AC, Xiang B, Gupta R, et al. THRIVE score predicts outcomes with a third-generation endovascular stroke treatment device in the TREVO-2 trial. Stroke. 2013;44:3370-5. doi: 10.1161/STROKEAHA.113.002796

15. Fan Y, Shi G, Wang S, et al. Prognostic outcome of intravenous thrombolysis in elderly patients aged ≥ 60 years with acute ischemic stroke by ASTRAL and THRIVE scales. J Thromb Thrombolysis. 2024;6. doi: 10.1007/s11239-024-03039-1

16. Shamalov NA, Chefranova ZY, Yarovaya EB, et al. Prognostic outcome of intravenous thrombolysis with non-immunogenic staphylokinase in patients aged ≥ 60 years with acute ischemic stroke by THRIVE scale. J Thromb Thrombolysis. 2025 Nov 16. doi: 10.1007/s11239-025-03212-0. Online ahead of print.

17. You JT, Hang Q, Xiao GD, et al. The role of THRIVE score in prediction of outcome of acute ischemie stroke patients with atrial fibrillation. Zhonghua Neike Zazhi. 2014;53:532-6.

18. Kuster GW, Dutra LA, Brasil IP, et al. Performance of four ischemic stroke prognostic scores in a Brazilian population. Arquivos de Neuro-Psiquiatria. 2016; 74:133-7. doi: 10.1590/0004-282X20160002

19. Kamel H, Patel N, Rao VA, et al. The totaled health risks in vascular events (THRIVE) score predicts ischemic stroke outcomes independent of thrombolytic therapy in the NINDS tPA trial. J Stroke Cerebrovasc Dis. 2013;22(7):1111-6. doi: 10.1016/j.jstroke-cerebrovasdis.2012.08.017

20. Flint AC, Faigeles BS, Cullen SP, et al. THRIVE score predicts ischemic stroke outcomes and thrombolytic hemorrhage risk in VISTA. Stroke. 2013;44(12):3365-9. doi: 10.1161/STROKEAHA.113.002794