Generate QR code
Open Access
Subscription Access
Modern thrombolytic drugs in the treatment of myocardial infarction, pharmacoinvasive approach
https://doi.org/10.30629/0023-2149-2025-103-7-499-505
Abstract
Despite the successes of modern medicine, retains one of the leading positions in the causes of disability and mortality. In order to improve the prognosis of patients with acute myocardial infarction, reduce the focus of necrosis, and reduce mortality, modern reperfusion therapy has been developed. This review examines the possible timing of thrombolysis, assessment of the relevance and features of the pharmacoinvasive approach in the treatment of acute myocardial infarction. Large randomized medical trials aimed at studying the effectiveness and safety of thrombolytic therapy were analyzed. We compared properties of thrombolytic drugs, their mechanism of action. The properties of an “ideal” thrombolytic were assessed. The advantages of the non-immunogenic staphylokinase drug- forteplase, are shown for use both stages — prehospital stage and in-hospital.
About the Authors
N. L. Vyazova
Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University) ; SM-Clinic LLC
Russian Federation
Russian Federation
Natalya L. Vyazova — cardiologist, assistant at the Department of Cardiology, X-ray endovascular and hybrid methods of diagnosis and treatment, Faculty of Additional Professional Education
Moscow
K. S. Lakhmai
SM-Clinic LLC
Russian Federation
Russian Federation
Kirill S. Lakhmai — X-ray endovascular surgeon
Moscow
M. N. Prostatov
SM-Clinic LLC
Russian Federation
Russian Federation
Maxim N. Prostatov — cardiovascular surgeon
Moscow
A. G. Koledinsky
Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University) ; SM-Clinic LLC
Russian Federation
Russian Federation
Anton G. Koledinsky — Doctor of Medical Sciences, Head of the Department of Cardiology, X-ray Endovascular and Hybrid Methods of Diagnostics and Treatment, Faculty of Additional Professional Education
Moscow
References
1. Russian Statistical Yearbook. 2019. Federal State Statistics Service (Rosstat). Moscow; 2019. (In Russian).
2. Russian statistical yearbook. 2022. (In Russian).
3. Passport of the national project National project “Demography”. 01.10.2021. (In Russian). URL: https://mintrud.gov.ru/ministry/programms/demography
4. Acute myocardial infarction with ST segment elevation of the electrocardiogram. Clinical guidelines 2020, Russian Cardiological Society. (In Russian). DOI: 10.15829/29/1560-4071-2020-4103
5. Keeley E.C., Boura Ju.A., Grines C.L. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13– 20. DOI: 10.1016/S0140-6736(03)12113-7
6. Neumann F-J., Sousa-Uva M., Ahlsson A., Alfonso F., Banning A.P., Benedetto U. et al. ESC Scientific Document Group. 2018 ESC/ EACTS Guidelines on myocardial revascularization. Eur. Heart. J. 2019;40:87–165. DOI: 10.1093/ejcts/ezy289
7. Fletcher A.P., Alkjaersing N., Smyrniotis F.E. et al. The treatment of patients suffering from early MI with massive and prolonged SK therapy. Trans. Assoc. Am. Phys. 1958;71:287–96.
8. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell’ Infarcto Miocardico (GISSI). Lancet. 1986;1:397–402. PMID: 2868337
9. Chazov E.I., Andreenko G.V. Experimental substantiation of therapy with lysis drugs. In the book: Meeting on the use of anticoagulants. L.; 1961. (In Russian).
10. Chazov E.I., Ruda M.Ya. Thrombolytic therapy for myocardial infarction. Cardiology. 1987;2:5–12. (In Russian).
11. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;2(8607):349–360. PMID: 2899772
12. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N. Engl. J. Med. 1993;329:673–682. DOI: 10.1056/NEJM199309023291001
13. Hasai B., Begar S., Wallentin L. et al. A prospective survey of the characteristics, treatment and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin. The Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur. Heart J. 2002;15(1):1190–2001. DOI: 10.1053/euhj.2002.3193
14. Gruppo italiano per lo studio della streptochinasi nell’ infarcto miocardico (GISSI). Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Lancet. 1987;2:871–874. PMID: 2889079
15. De Vreede J.J., Gorgels A.P., Verstraaten G.M. et al. Did prognosis after acute myocardial infarction change during the past 30 years? A meta-analysis. Journal of the American College of Cardiology. 1991;18:698–706, DOI: 10.1016/0735-1097(91)90792-8
16. Boersma E., Maas A.C., Deckers J.W., Simoons M.L. Early thrombolytic treatment in acute myocardial infarction: reappraiisal of the golden hour. Lancet 1996; 348: 771-775Stern R, Arntz H.R. Prehospital thrombolysis in acute myocardial infarction. Eur. J. Emerg. Med. 1998;5:471–479, PMID: 9919456
17. Acute myocardial infarction with ST segment elevation of the electrocardiogram. Clinical guidelines 2020. Russian Society of Cardiology (RSC). Russian Journal of Cardiology. 2020;25(11). (In Russian). DOI: 10.15829/29/1560-4071-2020-4103
18. Late assessment of thrombolytic efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction. Lancet. 1993; 342: 759-66. PMID: 8103874
19. Gershlic A.H., Stephens- Lioyd A., Hughes S et al. REACT Trial investigators, Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N. Engl. J. Med. 2005;353(26):2758– 68. DOI: 10.1056/NEJMoa050849
20. Bonnefoy E., Steg Ph.G., Boutitie F., Dubien P.-Y., Lapostolle F., Roncalli J., et al. Comparison of primary angioplasty and prehospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up. Eur. Heart J. 2009;30(13):1598–1606. DOI: 10.1093/eurheartj/ehp156. Epub 2009 May 8
21. The TIMI Research Group. The thrombolysis in myocardial infarction (TIMI) trial. Phase I Findings. N. Engl. J. Med. 1985;312:932–936. DOI: 10.1056/NEJM198504043121437
22. Pedley D.K. et al. Prospective observational cohort study of time saved by prehospital thrombolysis for ST elevation myocardial infarction delivered by paramedics. British Medical Journal. 2003;327:22–26. DOI: 10.1136/bmj.327.7405.22
23. Van de Werf F.J. et al. Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA. European Heart Journal. 2001;22:2253–2261. DOI: 10.1053/euhj.2001.2686
24. Van de Werf F.J. et al. The Task force on the management of acute myocardial infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal. 2003;24:28– 66. DOI: 10.1016/s0195-668x(02)00618-8
25. Weaver W.D. et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction. Journal of the American Medical Association. 1997;287:2093–2098. DOI: 10.1016/j.ahj.2010.10.033
26. Westerhout C.M. The influence of time from symptom onset and reperfusion strategy on 1-year survival in ST-elevation myocardial infarction: a pooled analysis of an early fibrinolytic strategy versus primary percutaneous coronary intervention from CAPTIM and WEST. American Heart Journal. 2011;161:283–290. DOI: 10.1016/j.ahj.2010.10.033
27. Borgia F., Goodman S.G., Halvorsen S. et al. Early routine percutaneous coronary intervention after fibrinolysis vs. standart therapy in ST segmeny elevation myocardial infarction: a metaanalysis. Eur. Heart J. 2010;31(17):2156–69. DOI: 10.1093/eurheartj/ehq204
28. D’Souza S.P., Mamas M.A., Fraser D.G., Fath- Ordoubadi F. Routine early coronary angioplasty versus ischaemia- guided angioplasty after thrombolysis in acute ST-elevation myocardial infarction: a meta-analysis Eur. Heart J. 2011;32(8):972–82. DOI: 10.1093/eurheartj/ehq398
29. Cantor W.J., Fitchett D., Borgundvaag B. et al, TRANSFER- AMI Trial Investigators. Routine early angioplasty after fibrnolysys for acute myocardial infarction. N. Engl. J. Med. 2009;360(26):2705– 18. DOI: 10.1056/NEJMoa0808276
30. Panchenko E.P. Thrombolytic drugs as a result of the treatment of acute myocardial infarction. Clinical Pharmacology. 2001;16. (In Russian).
31. Panchenko E.P. Antithrombotic therapy in cardiology. 2019:73. (In Russian). ISBN: 978-5-906499-592
32. Yusova E.I. Activation of plasminogen by low molecular weight streptokinase and the effect of fibrin. Biotechnologia acta. 2014;3:33–41. (In Russian).
33. Panchenko E. P. Thrombolytic drugs as a result of the treatment of acute myocardial infarction. Clinical Pharmacology. 2001:16–19. (In Russian).
34. Ruda M.Ya. et al. Diagnosis and treatment of patients with acute myocardial infarction with ST segment elevation of the electrocardiogram: clinical recommendations. Ministry of Health of the Russian Federation. 2013:60–64. (In Russian).
35. Mohammadi E., Mahnam K., Jahanian- Najafabadi A., Sadeghi M.H.M. Design and production of new chimeric reteplase with enhanced fibrin affinity: a theoretical and experimental study. J. Biomol. Struct. Dyn. 2021;39(4):1321–1333. DOI: 10.1080/07391102.2020.1729865
36. Martin U., Bader R., Böhm E., Kohnert U., von Möllendorf E., Fischer S., Sponer.G. BM 06.022: A novel recombinant plasminogen activator. Cardiovasc. Drug. Rev. 1993;22(3):299–311, DOI: 10.1111/j.1527-3466.1993.tb00193.x
37. McCartney P.J., Eteiba H., Maznyczka A.M., McEntegart M., Greenwood J.P., Muir D.F. et al. Low-dose intracoronary alteplase during primary percutaneous coronary intervention in patients with acute myocardial infarction: the T-TIME three-arm RCT. Efficacy Mech. Eval. 2020;7(5) DOI: 10.3310/eme07050
38. ASSENT-2 Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999;354:716–722. DOI: 10.1016/s0140-6736(99)07403-6
39. Sinnaeve P. et al. One-year follow-up of the ASSENT-2 trial: a double-blind, randomized comparison of a single-bolus tenecteplase and front-loaded alteplase in 16,949 patients with ST-elevation acute myocardial infarction. Am. Heart J. 2003;146:27–32. DOI: 10.1016/S0002-8703(03)00117-0
40. ASSENT-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001;358:605–613. DOI: 10.1016/S0140-6736(01)05775-0
41. Wallentin L. et al. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting. The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS Randomized Trial in Acute Myocardial Infarction. Circulation. 2003;108:135–142. DOI: 10.1161/01.CIR.0000081659.72985.A8
42. Markin S.S., Semenov A.M., Markov V.A. et al. Clinical study of the domestic fibrin-selective thrombolytic drug Fortelizin® (phase III). Bulletin of the Peoples’ Friendship University of Russia. Series: Medicine. 2012;(1):105–10. (In Russian).
43. Markov V.A., Duplyakov D.V., Konstantinov S.L. et al. Fortelysin® compared with Metalyse® in myocardial infarction with ST-segment elevation: results of the multicenter randomized study FREEDOM1. Cardiological Bulletin. 2017;12(3):52–9. (In Russian). DOI.org/10.15829/1560-4071-2018-11-110-116
44. Mazur E.S., Rabinovich R.M., Mazur V.V. and others. Comparative results of the use of recombinant non-immunogenic staphylokinase and tenecteplase in myocardial infarction with ST segment elevation in real clinical practice. Rational pharmacotherapy in cardiology. 2017;13(4):463–8. (In Russian). DOI:10.20996/1819-6446-2017-13-4-463-468.
45. Markov V.A., Duplyakov D.V., Konstantinov S.L. et al. Fortelysin® compared with Metalyse® in ST-segment elevation myocardial infarction: one-year results and clinical outcomes of the multicenter randomized trial FREEDOM1. Russian Journal of Cardiology. 2018;(11):110–6. (In Russian). DOI:10.15829/1560-4071-2018-11-110-116.
46. Kotamski M., Strandberg T.E., Nieminen M.S. Treatment of elderly patients with acute myocardial infarction. European Heart Journal. 2000;120 21:362. DOI: 10.1023/a:1025393209660
47. Markov V.A., Duplyakov D.V., Konstantinov S.L., Klein G.V., Aksentiev S.B., Platonov D.Yu. et al. Extended results of the use of the drug Fortelysin® in the FREEDOM1 study and real clinical practice. Russian Journal of Cardiology. 2022,27(8):5178. (In Russian). DOI: 10.15829/1560-4071-2022-5178
48. Armstrong P.W. et al. The strategic reperfusion early after myocardial infarction (STREAM) study. Am. Heart J. 2010;160:30–35(e31).
49. Gershlick A. et al. Impact of a pharmacoinvasive strategy when delays to primary PCI are prolonged. Heart. 2015;101:692–698.
50. Collen D. Staphylokinase: a potent, uniquely fibrin-selective thrombolytic agent. Nat. Med. 1998;4:279–84. DOI: 10.1038/nm0398-279
51. Sinnaeve P.R. et al. STEMI patients randomized to a pharmacoinvasive strategy or primary PCI: The STREAM 1-Year mortality follow-up. Circulation. 2014;130(14):1139–1145.
52. Welsh R.C. et al. Outcomes of a pharmacoinvasive strategy for successful versus failed fibrinolysis and primary percutaneous intervention in acute myocardial infarction (from the STrategic Reperfusion Early After Myocardial Infarction [STREAM] study). Am. J. Cardiol. 2014;114(6):811–819.
53. Markin S.S., Semenov A.M., Arzamascev E.V. et al. Fortelizyn® in patients with acute myocardial infarction. Medical Academic Journal. 2012;12(1):80–6. (In Russian).
Review
For citations:
Vyazova N.L., Lakhmai K.S., Prostatov M.N., Koledinsky A.G. Modern thrombolytic drugs in the treatment of myocardial infarction, pharmacoinvasive approach. Clinical Medicine (Russian Journal). 2025;103(7):499-505. (In Russ.) https://doi.org/10.30629/0023-2149-2025-103-7-499-505
Views:
34
Email this article 