Recombinant Albumin-free Streptokinase in Acute Myocardial Infarction: Pharmacovigilance Study (TIMES)
Keywords:
streptokinase, thrombolysis, pharmacovigilance, acute myocardial infarctionAbstract
Introduction: Acute myocardial infarction represents a public health problem in Cuba; it constitutes the main cause of morbidity and mortality. Fibrinolytic therapy with Heberkinase (recombinant streptokinase) has been effective and safe for this disease. The Center of Genetic Engineering and Biotechnology of Cuba developed a new formulation of recombinant streptokinase without albumin, to avoid the use of this hemoderivative.
Objective: To evaluate the safety of recombinant albumin-free streptokinase in the treatment of acute myocardial infarction under conditions of routine medical practice.
Methods: A pharmacovigilance and multicenter study was performed; the method of active monitoring during treatment and voluntary reporting was used. The protocol followed the guidelines of the Declaration of Helsinki. Adult patients who met the diagnostic and selection criteria were included and received 1,500,000 IU of recombinant albumin-free streptokinase intravenously. The information requested included: type of adverse event, duration, severity, outcome and causal relationship. A quantitative pharmacovigilance algorithm was applied to establish the degree of imputability. The proportion of each adverse reaction in the studied population was calculated.
Results: 213 patients were reported; 43.7% (93) with adverse events. The most frequent events were: arterial hypotension (30.0%), nausea (14.6%), vomiting (11.7%) and arrhythmias (6.1%). Eight patients died, whose causes were established to be of cardiac origin.
Conclusions: Thrombolysis with recombinant albumin-free streptokinase in acute myocardial infarction was safe and effective, with reduced mortality and associated complications.
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References
1. Organización Mundial de la Salud. Informe Mundial sobre Cardiopatía Isquémica 2020. Ginebra: OMS;2021 [acceso 15/05/2023]. Disponible en: https://www.paho.org/es/noticias/9-2-2020-oms-revela-principales-causas-muerte-discapacidad-mundo-2000-2019
2. Cuba. Ministerio de Salud Pública. Dirección Nacional de Estadísticas. Anuario Estadístico de Salud 2022. La Habana: MINSAP; 2023 [acceso 18/11/2023]. Disponible en: https://files.sld.cu/editorhome/files/2023/09/Anuario-Estadistico-de-Salud-2022-Ed-2023.pdf
3. Estrada MP, Hernández L, Pérez A, Rodríguez P, Serrano R, Rubiera R, et al. High level expression of streptokinase in Escherichia Coli. Biotechnology (NY). 1992;10:1138-42. DOI: https://doi.org/10.1038/nbt1092-1138
4. Toruncha A, Torres W, Mora E, León L, Padrón N, Castañeda M, et al. Comparative clinical trial in patients with acute myocardial infarction using recombinant and natural streptokinase. Biotecnología Aplicada. 1992;9:289-91. Disponible en: https://elfosscientiae.cigb.edu.cu/PDFs/Biotecnol%20Apl/1995/12/3/p%20194%20-%20195%20.pdf
5. The TERIMA Group Investigators. Multicenter, randomised, comparative study of recombinant vs. natural streptokinases in acute myocardial infarct. Thromb Haemost. 1999;82(6):1605-9. DOI:https://doi.org/10.1055/s-0037-1614886
6. The TERIMA Group of Investigator. TERIMA-2: national extension of thrombolytic treatment with recombinant streptokinase in acute myocardial infarct in Cuba. Thromb Haemost. 2000 [acceso 15/05/2023];84(6):949-54. Disponible en: https://europepmc.org/article/med/11330244
7. U.S. Department of Health and Human Services, National Institutes of Health, Common Terminology Criteriafor Adverse Events, Version 5.0; November 27, 2017 [acceso 15/05/2023]. Disponible en: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
8. Naranjo CA, Shear NH, Busto U. Adverse drug reactions. En: Kalant H, Roschlau WHE, editors. Principles of medical pharmacology. Oxford University Press, New York; 1998 [acceso 15/05/2023]:791-800. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK548069/
9. Betancourt BY, Marrero-Miragaya MA, Jiménez-López G, Valenzuela-Silva C, García-Iglesias E, Hernández-Bernal F, et al. Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction. BMC Clin Pharmacol. 2005;5(1):5. DOI: https://doi.org/10.1186/1472-6904-5-5
10. García-Abeijon P, Costa C, Taracido M, Herdeiro MT, Torre C, Figueiras A. Factors Associated with Underreporting of Adverse Drug Reactions by Health Care Professionals: A Systematic Review Update. Drug Saf. 2023;46(7):625-36. DOI: https://doi.org/10.1007/s40264-023-01302-7
11. Plueschke K, Jonker C, Strassmann V, Kurz X. Collection of Data on Adverse Events Related to Medicinal Products: A Survey Among Registries in the ENCePP Resources Database. Drug Saf. 2022;45(7):747-54. DOI: https://doi.org/10.1007/s40264-022-01188-x
12. GISSI-2: A factorial randomised trial of Alteplase versus Streptokinase and Heparin versus no Heparin among 12 490 patients with Acute Myocardial Infarction. Gruppo Italiano per lo Studio della sopravvivenza nell”infarto miocardico. Lancet. 1990;336(8707):65-71. DOI: https://doi.org/10.1016/0140-6736(90)91589-3
13. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: A randomised comparison of Streptokinase versus Tissue Plasminogen Activator versus Anistreplase and of Aspirin plus Heparin versus Aspirin alone among 41 229 cases of suspected Acute Myocardial Infarction. Lancet. 1992 [acceso 15/05/2023];339(8796):753-70. Disponible en https://pubmed.ncbi.nlm.nih.gov/2887430/
14. The GUSTO investigators. An International randomised trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329(10):673-82. DOI: https://doi.org/10.1056/NEJM199309023291001
15. Khalid K, Ahmad RE, Tong AYH, Lui SY, Abidin IZZ. Pathophysiology of streptokinase-induced hypotension in acute myocardial infarction: a systematic review of clinical evidence. Arch Med Sci Atheroscler Dis. 2021;6:e85-e94. DOI: https://doi.org/10.5114/amsad.2021
16. Abbasnezhad M, Shahnazarli G, Sadeghi MT, Parizad R, Aghdam NK, Nasiri B, et al. Evaluation of ventricular tachyarrhythmias in patients with myocardial infarction after streptokinase therapy. Cardiovasc Biomed J. 2021;1(1):1-7. DOI: https://doi.org/10.18502/cbj.v1i1.7510
17. Takada T, Shishido K, Hayashi T, Yokota S, Miyashita H, Yokoyama H, et al. Impact of Late Ventricular Arrhythmias on Cardiac Mortality in Patients with Acute Myocardial Infarction. J Interv Cardiol. 2019;1. DOI: https://doi.org/10.1155/2019/5345178
18. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology. Eur Heart J. Acute Cardiovascular Care. 2023;13(1):55-161. DOI: https://doi.org/10.1093/ehjacc/zuad156
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