Safety of prehospital thrombolysis with non-immunogenic staphylokinase in 51021 patients with ST-elevation myocardial infarction: data from the FRIDOM-registry

Aim. To evaluate real-world data on the safety of reperfusion therapy using non-immunogenic staphylokinase in a wide range of patients with STEMI at the prehospital stage.

Material and methods. FRIDOM-registry is a multicenter prospective non-interventional observational study. The registry included patients with an established diagnosis of STEMI who received reperfusion therapy with non-immunogenic staphylokinase (Fortelyzin®, OOO SupraGene, Russia) at a dose of 15 mg bolus or bolus-infusion. The safety criteria were all-cause inhospital mortality, major bleeding rate, and a combination of major adverse cardiac and cerebral events (MACCE) — all-cause death, cardiogenic shock, recurrent myocardial infarction, arrhythmia, heart failure deterioration, ischemic stroke, and intracranial hemorrhage during hospitalization. The rate and severity of bleedings were determined according to the BARC classification. The criterion for the effectiveness of reperfusion therapy was the coronary flow restoration according to electrocardiographic (ECG) data after 90 minutes. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice.

Results. Monitoring the use of non-immunogenic staphylokinase in STEMI from June 1, 2013 to January 14, 2025 covered 51021 patients. The mean age of patients included in the registry was 64,5±12,1 years; 17% of patients aged over 75 years; 70% of patients were male. A total of 96% of patients received thrombolysis at the prehospital stage. According to ECG, reperfusion within 90 minutes after thrombolysis was achieved in 74% of patients. All-cause mortality was 4,2%, of which 1,2% at the prehospital and 3,0% in the hospital stage. The major bleeding rate was 1,1%, intracranial hemorrhages — 1,1%; the minor bleeding rate was 3,2%. A subanalysis of patients included in the period 2019-2025 using the online platform FRIDOM-registry showed that in 2021 the MACCE rate in the group of patients without reperfusion significantly exceeded the values of other years (93% vs 36%, p<0,001), which could probably be due to the impact of the COVID-19 pandemic. In turn, the MACCE rate in the group of patients with reperfusion did not have significant fluctuations over the years and averaged 16±2% per year.

Conclusion. The real-world data obtained confirmed the high safety of non-immunogenic staphylokinase in 51021 patients, established earlier in clinical trials.

1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361(9351):13-20. doi:10.1016/S0140-6736(03)12113-7.

2. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-826. doi:10.1093/eurheartj/ehad191.

3. Staroverov II, Shakhnovich RM, Gilyarov MYu, et al. Eurasian clinical guidelines on diagnosis and treatment of acute coronary syndrome with ST segment elevation (STEMI). Eurasian heart journal. 2020;(1):4-77. (In Russ.) doi:10.38109/2225-1685-2020-1-4-77.

4. Averkov OV, Harutyunyan GK, Duplyakov DV, et al. 2024 Clinical practice guidelines for Acute myocardial infarction with ST segment elevation electrocardiogram. Russian Journal of Cardiology. 2025;30(3):6306. (In Russ.) doi:10.15829/1560-4071-2025-6306. EDN: IVJCUK.

5. 2020 Clinical practice guidelines for Acute ST-segment elevation myocardial infarction. Russian Journal of Cardiology. 2020;25(11):4103. (In Russ.) doi:10.15829/1560-4071-2020-4103.

6. Pinto DS, Kirtane AJ, Nallamothu BK, et al. Hospital Delays in Reperfusion for ST-Elevation Myocardial Infarction: Implications When Selecting a Reperfusion Strategy. Circulation. 2006;114(19):2019-25. doi:10.1161/CIRCULATIONAHA.106.638353.

7. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J Acute Cardiovasc Care. 2024;13(1):55-161. doi:10.1093/ehjacc/zuad107.

8. Morrison LJ, Verbeek PR, McDonald AC, et al. Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis. JAMA. 2000;283:2686-892. doi:10.1001/jama.283.20.2686.

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

10. 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.

11. Verstraete M. Third-Generation Thrombolytic Drugs. Am J Med. 2000;109:52-58. doi:10.1016/s0002-9343(00)00380-6.

12. Toul M, Nikitin D, Marek M, et al. Extended mechanism of the plasminogen activator staphylokinase revealed by global kinetic analysis: 1000-fold higher catalytic activity than that of clinically used alteplase. ACS Catal. 2022;12:3807-14. doi:10.1021/acscatal.1c05042.

13. Markin SS, Semenov AM, Arzamascev EV, et al. Fortelizyn in patients with acute myocardial infarction. Medical Academic Journal. 2012;12(1):80-6. (In Russ.)

14. Markin SS, Semenov AM, Markov VA, et al. Clinical trial of fibrinselective thrombolytic pharmaceutical agent FORTELYZIN (III Phase). Rudn J Med. 2012;(1):105-10. (In Russ.)

15. Markov VA, Duplyakov DV, Konstantinov SL, et al. Fortelyzin® versus Metalyse® in ST-segment elevation myocardial infarction: results of multicenter randomized trial FRIDOM 1. Kardiologicheskyi vestnik. 2017;12(3):52-9. (In Russ.)

16. Markov VA, Duplyakov DV, Konstantinov SL, et al. Fortelyzin in comparison with Metalyse for ST-elevated myocardial infarction: one-year results and clinical outcomes of a multicenter randomized study FRIDOM1. Russian Journal of Cardiology. 2018;(11): 110-6. (In Russ.) doi:10.15829/1560-4071-2018-11-110-116.

17. Vishlov EV, Alekseeva YaV, Gerasimets ЕА, Markov VA. Experimental and clinical studies of staphylokinase and Fortelyzin®. Kardiologiya: Novosti. Mneniya. Obuchenie. 2017; 2(13):57-61. (In Russ.)

18. Mazur ES, Rabinovich RM, Mazur VV, et al. The results of use of new native thrombolytic in clinical practice. Rational Pharmacotherapy in Cardiology. 2017;13(4):463-8. (In Russ.) doi:10.20996/18196446-2017-13-4-463-468.

19. Alekseeva YaV, Vyshlov EV, Markov VA. Recombinant non-immunogenic staphylokinase in the treatment of patients with acute myocardial infarction. Siberian Journal of Clinical and Experimental Medicine. 2016;31(2):51-4. (In Russ.) doi:10.29001/2073-8552-2016-31-2-51-54.

20. Mazur ES, Rabinovich RM, Mazur VV, et al. The results of use of new native thrombolytic in clinical practice. Rational Pharmacotherapy in Cardiology. 2016;12(2):160-5. (In Russ.) doi:10.20996/1819-6446-2016-12-2-160-165.

21. Vatutin NT, Kostogryz VB, Kostogryz AI, et al. Effectiveness of thrombolysis by non-immunogenic staphylokinase in patient with ST-elevation myocardial infarction. Russian Journal of Cardiology. 2016;(10):105-6. (In Russ.) doi:10.15829/1560-4071-2016-10-105-106.

22. Koledinsky AG, Mikheeva YuV, Semenov AM, et al. Mid-term clinical results of thrombolytic drugs Fortelyzin® and Metalyse® in the FRIDOM1 study as a part of pharmacoinvasive strategy for ST-segment elevation myocardial infarction. International Journal of Interventional Cardioangiology. 2021;65:19-35. (In Russ.)

23. Markov VA, Duplyakov DV, Konstantinov SL, et al. Advanced results of Fortelyzin® use in the FRIDOM1 study and real clinical practice. Russian Journal of Cardiology. 2022; 27(8):5178. (In Russ.) doi:10.15829/1560-4071-2022-5178.

24. Thygesen K, Alpert JS, Jaffe AS, et al.; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018;72(18):2231-64. doi:10.1016/j.jacc.2018.08.1038.

25. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123:2736-47. doi:10.1161/CIRCULATIONAHA.110.009449.

26. Peiyuan H, Jingang Y, Haiyan X, et al. The Comparison of the Outcomes between Primary PCI, Fibrinolysis, and No Reperfusion in Patients ≥75 Years Old with ST-Segment Elevation Myocardial Infarction: Results from the Chinese Acute Myocardial Infarction (CAMI) Registry. PLoS One. 2016;11(11):e0165672. doi:10.1371/journal.pone.0165672.

27. Czarnecki A, Welsh RC, Yan RT, et al. Reperfusion strategies and outcomes of ST-segment elevation myocardial infarction patients in Canada: observations from the Global Registry of Acute Coronary Events (GRACE) and the Canadian Registry of Acute Coronary Events (CANRACE). Canadian Journal of Cardiology. 2012;28(1):40-7. doi:10.1016/j.cjca.2011.09.011.

28. Koh HP, Redzuan MdA, Mohd Saffian S, et al. Impact of COVID-19 pandemic on STEMI thrombolysis and Emergency Department'sperformance in anon-PCI capable tertiary hospital. American Journal of Emergency Medicine. 2022;60:9-14. doi:10.1016/j.ajem.2022.07.021.

29. Goel A, Malik AH, Bandyopadhyay D, et al. Impact of COVID-19 on Outcomes of Patients Hospitalized With STEMI: A Nationwide Propensity-matched Analysis. Current Problems of Cardiology. 2023;48(4):101547. doi:10.1016/j.cpcardiol.2022.101547.

30. Baytuğan NZ, Kandemir HÇ, Bezgin T. In-Hospital Outcomes of ST-Segment Elevation Myocardial Infarction in COVID-19 Positive Patients Undergoing Primary Percutaneous Intervention. Arquivos Brasileiros de Cardiologia. 2024;121(1):e20230258. doi:10.36660/abc.20230258.

31. Kiris T, Avci E, Ekin T, et al. Impact of COVID-19 outbreak on patients with ST-segment elevation myocardial ınfarction (STEMI) in Turkey: results from TURSER study (TURKISH St-segment elevation myocardial ınfarction registry). Journal of Thrombosis and Thrombolysis. 2022;53(2):321-4. doi:10.1007/s11239-021-02487-3.

32. Das MK, Malviya A, Zachariah G, et al. Gender bias in acute myocardial infarction care in India: Nationwide retrospective study of 41832 patients. Indian Heart J. 2025;77(1): 22-7. doi:10.1016/j.ihj.2025.01.001.

33. Boytsov SA, Shakhnovich RM, Tereschenko SN, et al. Features of the reperfusion therapy for ST-Segment elevation myocardial infarction according to the Russian Registry of Acute Myocardial Infarction — REGION-IM. Kardiologiia. 2024;64(2):3-17. (In Russ.) doi:10.18087/cardio.2024.2.n2601.

34. 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 Neurol. 2021;20:721-8. doi:10.1016/S1474-4422(21)00210-6.

35. Gusev EI, Martynov MYu, Shamalov NA, et al. Non-immunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results). S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(7):56-65. (In Russ.) doi:10.17116/jnevro202212207156.

36. Kirienko AI, Leontyev SG, Yarovaya EB, et al. Non-immunogenic staphylokinase — a thrombolytic agent in the treatment of massive pulmonary embolism: results of the FORPE clinical trial. Russian Journal of Cardiology. 2024;29(11):6157. (In Russ.) doi:10.15829/1560-4071-2024-6157.

37. Kirienko AI, Leontyev SG, Tereschenko SH, et al. Non-immunogenic recombinant staphylokinase versus alteplase for patients with massive pulmonary embolism: a randomised open-label, multicenter, parallel-group, non-inferiority trial FORPE. Journal of Thrombosis and Haemostasis. 2025;23(2):657-67. doi:10.1016/j.jtha.2024.09.035.

38. Tereshchenko SN, Yarovaya EB, Leontiev SG, et al. Non-immunogenic staphylokinase in patients with massive intermediate-high risk pulmonary embolism: protocol of the FORPE-2 multicenter, double-blind, randomized, placebo-controlled trial. Russian Journal of Cardiology. 2025;30(2):6291. (In Russ.) doi:10.15829/1560-4071-2025-6291.

39. Zatevakhin II, Chupin AV, Karpenko AA, et al. Intraarterial intrathrombus thrombolysis with non-immunogenic staphylokinase vs surgery in patients with acute limb ischemia: protocol of a multicenter, open-label, randomized clinical trial FORAT. Angiology and Vascular Surgery. Journal named after Academician A. V. Pokrovsky. 2025;31(2):33-41. (In Russ.) doi:10.33029/1027-6661-2025-31-2-33-41.