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Thrombolytic therapy with Revelisa in ischemic stroke: results of the PRIMA international multicenter observational study

https://doi.org/10.14412/2074-2711-2025-1-57-66

Abstract

Thrombolytic therapy (TLT) of ischemic stroke (IS) with alteplase within the first 4.5 hours from the onset of symptoms is the most effective and proven method of treatment.

Objective: to evaluate the safety and efficacy of TLT with Revelisa (alteplase) in IS in real-world clinical practice.

Material and methods. The results of TLT with Revelisa were analyzed in 1181 patients with IS: 616 (52.2%) women and 565 (47.8%) men (mean age 68.28±12.56 years), of which 140 (11.9%) with staged reperfusion. The mean time from disease onset to TLT was 2.58±0.83 hours. The Heidelberg classification was used to assess hemorrhages during neuroimaging. Symptomatic hemorrhagic transformation (HT) was defined according to ECASS III criteria. The study group was characterized by high comorbidity: arterial hypertension (96.9%), ischemic heart disease (56.7%), chronic heart failure (55.8%) and cardiac arrhythmias (33.3%) were most common; diabetes mellitus was present in 23% of patients. IS occurred repeatedly in 15.4% of cases.

Results. An improvement of 4 points or more on the NIHSS scale one day after TLT was observed in 41% of patients. The dynamics of the decrease in neurological symptoms one day later and at the time of discharge were statistically significant (p<0.001). The hospital mortality rate for the entire group was 8%, for the TLT group without endovascular intervention 5.6%. Twenty-nine patients (2.46%) had symptomatic HT, 14 of whom underwent endovascular intervention. The proportion of patients with a favorable clinical outcome (0–2 points on the modified Rankin scale) at discharge and at day 90 was 50.1% and 65.5%, respectively. Conclusion. The results of the PRIMA study confirm the high level of efficacy and safety of Revelisa in patients with IS, including during staged reperfusion. The data obtained are consistent with the published registry studies on alteplase in IS.><0.001). The hospital mortality rate for the entire group was 8%, for the TLT group without endovascular intervention 5.6%. Twenty-nine patients (2.46%) had symptomatic HT, 14 of whom underwent endovascular intervention. The proportion of patients with a favorable clinical outcome (0–2 points on the modified Rankin scale) at discharge and at day 90 was 50.1% and 65.5%, respectively.

Conclusion. The results of the PRIMA study confirm the high level of efficacy and safety of Revelisa in patients with IS, including during staged reperfusion. The data obtained are consistent with the published registry studies on alteplase in IS.

About the Authors

N. A. Shamalov
Federal Center of Brain Research and Neurotechnologies, Federal Medical and Biological Agency
Russian Federation

1, Ostrovityanova St., Build. 10, Moscow, 117513


Competing Interests:

The conflict of interests did not affect the results of the study



D. R. Khasanova
Interregional Clinical and Diagnostic Center; Kazan State Medical University, the Ministry of Health of Russia
Russian Federation

12a, Karbysheva St., Kazan 420101

49, Butlerova St., Kazan 420012


Competing Interests:

The conflict of interests did not affect the results of the study



S. V. Marchenko
Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology, Republic of Belarus
Belarus

8, Semashko St., Minsk 220087


Competing Interests:

The conflict of interests did not affect the results of the study



M. A. Soldatov
Federal Center of Brain Research and Neurotechnologies, Federal Medical and Biological Agency
Russian Federation

Mikhail Anatolyevich Soldatov

1, Ostrovityanova St., Build. 10, Moscow 117513


Competing Interests:

The conflict of interests did not affect the results of the study



T. P Alekseeva
City Clinical Hospital named after S.S. Yudin, Moscow Healthcare Department
Russian Federation

4, Kolomensky Proezd, Moscow 115446


Competing Interests:

The conflict of interests did not affect the results of the study



O. V. Androfagina
Samara Regional Clinic Hospital named after V.D. Seredavin
Russian Federation

159, Tashkentskaya St., Samara 443095


Competing Interests:

The conflict of interests did not affect the results of the study



L. N. Antipova
Regional Clinical Hospital No. 2, Ministry of Health of the Krasnodar Krai
Russian Federation

130, Tamanskaya St., Krasnodar 350001


Competing Interests:

The conflict of interests did not affect the results of the study



L. I. Anishchenko
Regional Clinical Hospital
Russian Federation

40, Kalinina St., Khanty-Mansiysk 628012


Competing Interests:

The conflict of interests did not affect the results of the study



E. M. Beketova
Samara City Clinical Hospital No. 1 named after N.I. Pirogov
Russian Federation

80, Polevaya St., Samara 443096


Competing Interests:

The conflict of interests did not affect the results of the study



A. A. Bulanov
Penza Regional Clinical Hospital named after N.N. Burdenko
Russian Federation

28, Lermontova St., Penza 440026


Competing Interests:

The conflict of interests did not affect the results of the study



A. V. Gerasimova
Republican Hospital No. 1 – National Center of Medicine named after M.E. Nikolaev
Russian Federation

4, Sergelyakhskoye Shosse, Yakutsk 677010


Competing Interests:

The conflict of interests did not affect the results of the study



N. Kh. Gorst
City Clinical Hospital named agfter I.V. Davydovsky, Moscow Healthcare Department
Russian Federation

11/6, Yauzskaya St., Moscow 109240


Competing Interests:

The conflict of interests did not affect the results of the study



A. G. Gutsalyuk
City Clinical Hospital named after A.K. Yeramishantsev, Moscow Healthcare Department
Russian Federation

15, Lenskaya St. Moscow 129327


Competing Interests:

The conflict of interests did not affect the results of the study



T. V. Demin
Interregional Clinical and Diagnostic Center
Russian Federation

12a, Karbysheva St., Kazan 420101


Competing Interests:

The conflict of interests did not affect the results of the study



A. V. Dyudin
City Hospital No. 26
Russian Federation

2, Kostyushko St., St. Petersburg 196247


Competing Interests:

The conflict of interests did not affect the results of the study



U. A. Yelemanov
Kaluga Regional Clinical Hospital
Russian Federation

1, Vishnevskogo St., Kaluga 248007


Competing Interests:

The conflict of interests did not affect the results of the study



A. R. Zakaryaeva
City Clinical Hospital named after V.V. Veresaev, Moscow Healthcare Department
Russian Federation

10, Lobnenskaya St., Moscow 127644


Competing Interests:

The conflict of interests did not affect the results of the study



N. N. Zinovyeva
City Clinical Hospital No. 1
Russian Federation

16, Vorovskogo St., Chelyabinsk 454092


Competing Interests:

The conflict of interests did not affect the results of the study



S. S. Ziborova
Novokuznetsk City Clinical Hospital No. 1 named after G.P. Kurbatov
Russian Federation

28, Bardina Prosp., Novokuznetsk 654057


Competing Interests:

The conflict of interests did not affect the results of the study



D. N. Kazakov
Kommunarka Moscow Multidisciplinary Clinical Center, Moscow Healthcare Department
Russian Federation

8, Sosensky Stan St., Kommunarka Settlement, Sosenskoye Settlement, Moscow 108814


Competing Interests:

The conflict of interests did not affect the results of the study



N. V. Komissarova
First Republican Clinical Hospital, Ministry of Health of the Ural Region
Russian Federation

57, Votkinskoye Shosse, Izhevsk 426039


Competing Interests:

The conflict of interests did not affect the results of the study



I. V. Korobeynikov
Irkutsk Regional Clinical Hospital, winner of the “Mark of the Honor” award
Russian Federation

100, Yubileyny Microdistrict, Irkutsk 664049


Competing Interests:

The conflict of interests did not affect the results of the study



K. V. Korovashkova
City Clinical Hospital No. 67 named after L.A. Vorokhobov, Moscow Healthcare Department
Russian Federation

2/44, Salyama Adilya St., Moscow 123423


Competing Interests:

The conflict of interests did not affect the results of the study



E. L. Kuzmin
Novgorod Regional Clinical Hospital
Russian Federation

14, Pavla Levitta St., Veliky Novgorod 173008


Competing Interests:

The conflict of interests did not affect the results of the study



A. A. Kulesh
City Clinical Hospital No. 4
Russian Federation

2, KIM St., Perm 614107


Competing Interests:

The conflict of interests did not affect the results of the study



R. R. Kuliev
City Clinical Hospital named after A.K. Yeramishantsev, Moscow Healthcare Department
Russian Federation

15, Lenskaya St. Moscow 129327


Competing Interests:

The conflict of interests did not affect the results of the study



A. S. Lebedev
City Clinical Hospital No. 13, Moscow Healthcare Department
Russian Federation

1/1, Velozavodskaya St., Moscow 115280


Competing Interests:

The conflict of interests did not affect the results of the study



A. L. Lukyanov
City Clinical Hospital No. 31 named after Academician G.M. Savelyeva, Moscow Healthcare Department
Russian Federation

42, Lobachevskogo St., Moscow 119415


Competing Interests:

The conflict of interests did not affect the results of the study



V. I. Maksimov
Republican Hospital named after V.A. Baranov
Russian Federation

3, Pirogova St., Petrozavodsk 185002


Competing Interests:

The conflict of interests did not affect the results of the study



O. I. Mikhaylenko
City Clinical Hospital No. 34
Russian Federation

18, Titova St., Novosibirsk 630054


Competing Interests:

The conflict of interests did not affect the results of the study



I. V. Moldavskaya
Kuzbass Clinical Cardiology Center named after L.S. Barbarash
Russian Federation

6, Sosnovy Boulevard, Kemerovo 650002


Competing Interests:

The conflict of interests did not affect the results of the study



D. M. Murtazalieva
City Clinical Hospital named after V.V. Veresaev, Moscow Healthcare Department
Russian Federation

10, Lobnenskaya St., Moscow 127644


Competing Interests:

The conflict of interests did not affect the results of the study



Yu. S. Mukhamadieva
Emergency Medicine Center
Russian Federation

18, Naberezhnochelninsky Prosp., Naberezhnye Chelny 423803


Competing Interests:

The conflict of interests did not affect the results of the study



V. N. Nesterova
Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko
Russian Federation

190, Rodionova St., Nizhny Novgorod 603093


Competing Interests:

The conflict of interests did not affect the results of the study



D. G. Novikov
Bryansk Regional Hospital No. 1
Russian Federation

86, Stanke Dimitrova Prosp., Bryansk 241050


Competing Interests:

The conflict of interests did not affect the results of the study



S. V. Platunova
Surgut Clinical Traumatological Hospital
Russian Federation

20, Nefteyuganskoe Shosse, Surgut 628418


Competing Interests:

The conflict of interests did not affect the results of the study



E. P. Prudius
Rostov Regional Clinical Hospital
Russian Federation

170, Blagodatnaya St., Rostov-on-Don 344015


Competing Interests:

The conflict of interests did not affect the results of the study



R. A. Rayemgulov
Neuro-Praktika LLC
Russian Federation

70, Gubernskaya St., Tyumen 625032


Competing Interests:

The conflict of interests did not affect the results of the study



V. A. Saskin
First City Clinical Hospital named after E.E. Volosevich
Russian Federation

1, Suvorova St., Arkhangelsk 163001


Competing Interests:

The conflict of interests did not affect the results of the study



A. V. Sinelshchikova
Smolensk Regional Clinical Hospital
Russian Federation

27, Gagarina Prosp., Smolensk 214018


Competing Interests:

The conflict of interests did not affect the results of the study



E. A. Strautmanis
City Clinical Hospital of Emergency Medicine No. 1
Russian Federation

9, Pereleta St., Omsk 644112


Competing Interests:

The conflict of interests did not affect the results of the study



V. S. Suryakhin
City Clinical Hospital named after V.M. Buyanov, Moscow Healthcare Department
Russian Federation

26, Bakinskaya St., Moscow 115516


Competing Interests:

The conflict of interests did not affect the results of the study



E. V. Tavlueva
City Clinical Hospital named after F.I. Inozemtsev, Moscow Healthcare Department
Russian Federation

1, Fortunatovskaya St., Moscow 105187


Competing Interests:

The conflict of interests did not affect the results of the study



Yu. A. Telyatnik
Research Institute – Regional Clinical Hospital No. 1 named after S.V. Ochapovsky
Russian Federation

167, Pervogo Maya St., Krasnodar 350086


Competing Interests:

The conflict of interests did not affect the results of the study



N. V. Halo
Krasnoyarsk Interdistrict Clinical Hospital No. 20 naned after I.S. Berzon
Russian Federation

12, Instrumentalnaya St., Krasnoyarsk 660123


Competing Interests:

The conflict of interests did not affect the results of the study



M. S. Cherepyansky
Komi Republican Clinical Hospital, Syktyvkar
Russian Federation

114, Pushkina St., Syktyvkar 167004


Competing Interests:

The conflict of interests did not affect the results of the study



N. A. Marskaya
Federal Center of Brain Research and Neurotechnologies, Federal Medical and Biological Agency
Russian Federation

1, Ostrovityanova St., Build. 10, Moscow 117513


Competing Interests:

The conflict of interests did not affect the results of the study



References

1. Feigin VL, Brainin M, Norrving B, et al. World Stroke Organization (WSO): Global Stroke Fact Sheet 2022. Int J Stroke. 2022 Jan;17(1):18- 29. doi: 10.1177/17474930211065917. Erratum in: Int J Stroke. 2022 Apr;17(4):478. doi: 10.1177/17474930221080343

2. Ignatyeva VI, Voznyuk IA, Shamalov NA, et al. Social and economic burden of stroke in Russian Federation. Zhurnal nevrologii i psihiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(8-2):5-15. doi: 10.17116/jnevro20231230825 (In Russ.).

3. World Health Organization. The top 10 causes of death. Available at: https://www.who.int/news-room/factsheets/detail/the-top-10-causes-of-death (accessed 14.01.2025).

4. Number of deaths by causes of death. Demography. Federal State Statistics Service. Available at: https://rosstat.gov.ru/folder/12781 (accessed 14.01.2025) (In Russ.)].

5. Rathore SS, Hinn AR, Cooper LS, et al. Characterization of incident stroke signs and symptoms: findings from the atherosclerosis risk in communities study. Stroke. 2002 Nov;33(11):2718-21. doi: 10.1161/01.str.0000035286.87503.31

6. Slujitoru AS, Enache AL, Pintea IL, et al. Clinical and morphological correlations in acute ischemic stroke. Rom J Morphol Embryol. 2012;53(4):917-26.

7. Barbay M, Taillia H, Nedelec-Ciceri C, et al. Prevalence of Poststroke Neurocognitive Disorders Using National Institute of Neurological Disorders and Stroke-Canadian Stroke Network, VASCOG Criteria (Vascular Behavioral and Cognitive Disorders), and Optimized Criteria of Cognitive Deficit. Stroke. 2018 May;49(5):1141-7. doi: 10.1161/STROKEAHA.117.018889. Epub 2018 Apr 11.

8. GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. Epub 2021 Sep 3.

9. Collen D, Lijnen HR. The tissue-type plasminogen activator story. Arterioscler Thromb Vasc Biol. 2009 Aug;29(8):1151-5. doi: 10.1161/ATVBAHA.108.179655

10. Reed BR, Chen AB, Tanswell P, et al. Low incidence of antibodies to recombinant human tissue-type plasminogen activator in treated patients. Thromb Haemost. 1990 Oct 22;64(2):276-80.

11. Hacke W, Donnan G, Fieschi C, et al; ATLANTIS Trials Investigators; ECASS Trials Investigators; NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004 Mar 6;363(9411):768-74. doi: 10.1016/S0140-6736(04)15692-4

12. Hacke W, Kaste M, Bluhmki E, et al; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317- 29. doi: 10.1056/NEJMoa0804656

13. Emberson J, Lees KR, Lyden P, et al; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5.

14. Muruet W, Rudd A, Wolfe CDA, Douiri A. Long-Term Survival After Intravenous Thrombolysis for Ischemic Stroke: A Propensity Score-Matched Cohort With up to 10-Year Follow-Up. Stroke. 2018 Mar;49(3):607-13. doi: 10.1161/STROKEAHA.117.019889. Epub 2018 Feb 12.

15. Clinical recommendations “Ischemic stroke and transient ischemic attack in adults”. 2021. Available at: https://cr.minzdrav.gov.ru/recommend/171_2 (accessed 12.11.2024) (In Russ.).

16. Berge E, Whiteley W, Audebert H, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021 Mar;6(1):I-LXII. doi: 10.1177/2396987321989865. Epub 2021 Feb 19.

17. Mead GE, Sposato LA, Sampaio Silva G, et al. A systematic review and synthesis of global stroke guidelines on behalf of the World Stroke Organization. Int J Stroke. 2023 Jun;18(5):499- 531. doi: 10.1177/17474930231156753. Epub 2023 Mar 1.

18. Rules for conducting research on biological medicinal products of the Eurasian Economic Union: decision of the Council of the Eurasian Economic Commission №89 from 03.11.2016. Moscow; 2016. Available at: https://www.garant.ru/products/ipo/prime/doc/71446406 (accessed 14.01.2025) (In Russ.).

19. Gusarova VD, Pantyushenko MS, Simonov VM, et al. Physico-Chemical and Biological Properties of Biosimilar and Reference Tissue Plasminogen Activator Products. BIOpreparaty. Profilaktika, diagnostika, lechenie = BIOpreparations. Prevention, Diagnosis, Treatment. 2019;19(1):39-49. doi: 10.30895/2221-996X-2019-19-1-39-49 (In Russ.).

20. Kokorin VA, Markova OA, Gordeev IG, et al. Comparative safety and efficacy study of Russian recombinant tissue plazminogen activator Revelisa® in patients with myocardial infarction. Terapiya = Therapy. 2019;(2):42-56. doi: 10.18565/therapy.2019.2.42-57 (In Russ.).

21. Chashchinova DV, Shamonov NA, Vassarais RA, Kudlai DA. Development of a highly efficient technology for purificationof recombinant tissue plasminogen activator. Farmatsiya = Pharmacy. 2019;68(4):39-46. Available at: https://pharmaciyajournal.ru/25419218-2019-04-06 (In Russ.).

22. Soldatov MA, Klimov LV, Tolmachev AP, et al. Intravenous thrombolytic therapy of ischemic stroke with the drug Revelisa in real clinical practice: results of the IVT-AIS-R study. Zhurnal nevrologii i psihiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(12-2):1- 8. doi: 10.17116/jnevro20221221221 (In Russ.).

23. Murtazalieva DM, Zakar'yaeva AR, Soshina TD, et al. Experience of using a Russian alteplase product as thrombolytic therapy in patients with ischemicstroke in routine practice. Zhurnal nevrologii i psihiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(8-2):1-5. doi: 10.17116/jnevro20231230821 (In Russ.).

24. Marchenko SV, Hil UV, Hil IG. Comparative characteristics of the efficacy and safety of the original alteplase and its complete biosimilar in the treatment of ischemic stroke in real clinical practice. Zhurnal nevrologii i psihiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2024;124(3-2):49-54. doi: 10.17116/jnevro202412403249 (In Russ.).

25. Resolution of the Ministry of Health of the Republic of Belarus 01/18/2018 No. 8 “On approval of the clinical protocol “Diagnosis and treatment of patients with diseases of the nervous system (adult population)” (In Russ.).

26. General characteristics of the medicinal product Reveliza LP-No. (004035)-(RG-RU) dated 18.12.2023. Available at: https://www.generium.ru/products/reveliza-mnn-alteplaza (accessed 14.01.2025) (In Russ.).

27. Yaghi S, Willey JZ, Cucchiara B, et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Quality of Care and Outcomes Research. 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 Dec;48(12):e343-e361. doi: 10.1161/STR.0000000000000152. Epub 2017 Nov 2.

28. Khasanova DR, Kalinin MN, Ibatullin MM, Rakhimov ISh. The haemorrhagic transformation of cerebral infarction: classification, pathogenesis, predictors and effect on the functional outcome. Annaly klinicheskoj i jeksperimental'noj nevrologii = Annals of Clinical and Experimental Neurology. 2019;13(2):47-59. doi: 10.25692/ACEN.2019.2.6 (In Russ.).

29. Shamalov NA. Reperfusion therapy for ischemic stroke in the Russian Federation: Problems and promises. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2014;6(2S):15- 22. doi: 10.14412/2074-2711-2014-2S-15-22 (In Russ.).

30. Wahlgren N, Ahmed N, Davalos A, et al; SITS-MOST investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007 Jan 27;369(9558):275-82. doi: 10.1016/S0140-6736(07)60149-4. Erratum in: Lancet. 2007 Mar 10;369(9564):826.

31. Wahlgren N, Ahmed N, Davalos A, et al; SITS investigators. Thrombolysis with alteplase 3–4.5 h after acute ischaemic stroke (SITSISTR): an observational study. Lancet. 2008 Oct 11;372(9646):1303-9. doi: 10.1016/S0140-6736(08)61339-2. Epub 2008 Sep 12.


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For citations:


Shamalov NA, Khasanova DR, Marchenko SV, Soldatov MA, Alekseeva TP, Androfagina OV, Antipova LN, Anishchenko LI, Beketova EM, Bulanov AA, Gerasimova AV, Gorst NK, Gutsalyuk AG, Demin TV, Dyudin AV, Yelemanov UA, Zakaryaeva AR, Zinovyeva NN, Ziborova SS, Kazakov DN, Komissarova NV, Korobeynikov IV, Korovashkova KV, Kuzmin EL, Kulesh AA, Kuliev RR, Lebedev AS, Lukyanov AL, Maksimov VI, Mikhaylenko OI, Moldavskaya IV, Murtazalieva DM, Mukhamadieva YS, Nesterova VN, Novikov DG, Platunova SV, Prudius EP, Rayemgulov RA, Saskin VA, Sinelshchikova AV, Strautmanis EA, Suryakhin VS, Tavlueva EV, Telyatnik YA, Halo NV, Cherepyansky MS, Marskaya NA. Thrombolytic therapy with Revelisa in ischemic stroke: results of the PRIMA international multicenter observational study. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2025;17(1):57-66. (In Russ.) https://doi.org/10.14412/2074-2711-2025-1-57-66

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)