Multicenter, Randomized, Comparative Study of Recombinant vs. Natural Streptokinases in Acute Myocardial Infarct (TERIMA)

The TERIMA Group Investigators

doi:10.1055/s-0037-1614886

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(06): 1605-1609
DOI: 10.1055/s-0037-1614886

Rapid Communication

Schattauer GmbH

Multicenter, Randomized, Comparative Study of Recombinant vs. Natural Streptokinases in Acute Myocardial Infarct (TERIMA)

Authors

The TERIMA Group Investigators

Abstract

Summary

Aim: To compare the effects on hemostasis and coronary patency of recombinant (rSK) and natural (nSK) streptokinases in patients with acute myocardial infarct (AMI). Methods: Patients from 7 hospitals, <70 years old, less than 12 h after the onset of AMI symptoms, with ST segment elevation or bundle branch block, without contraindications for thrombolytic therapy, were randomized to receive 1.5 million units of nSK or rSK in a one-hour intravenous infusion. Fibrinogen, fibrinogen degradation products (FDP) and thrombin time were monitored. A coronary angiography was performed after 5-10 days in those patients who gave their consent and did not refer allergy to iodine contrasts. Images were blindly evaluated by an independent committee. Results: 224 patients were randomized (113 nSK and 111 rSK). Groups were equivalent in all baseline and demographic variables except that rSK patients were 5.4 years significantly older. They were also comparable in all the clinical characteristics. Both treatments produced the same changes in hemostasis. Fibrinogen levels decreased, FDP and thrombin time increased immediately after thrombolysis and returned to baseline 2 days afterwards, but fibrinogen values continued to increase up to day 10. Coronary patency (TIMI 2-3) rates at 7.8 ± 2.7 and 8.0 ± 2.7 days after fibrinolysis were 70.7% and 67.1% for nSK and rSK groups, respectively (non-significant difference). Hypotension and arrhythmias were the most frequent adverse events in both groups, which did not differ in this respect either. Five patients from each group died, one of them (nSK) due to gastroduodenal bleeding probably related to treatment. Conclusions: rSK behaved similarly to nSK regarding coronary patency at 8 days after thrombolysis and the changes induced on fibrinogen, FDP and thrombin time. These results suggest that the same benefit/risk profile reported for AMI patients treated with nSK can be expected for rSK.

A list of the “Trombolisis con Estreptoquinasa Recombinante en el Infarto del Miocardio Agudo” (Thrombolysis with Recombinant Streptokinase in Acute Myocardial Infarct) investigators appears in the Appendix, p. 1608.

Key Words

Streptokinase - thrombolysis - acute myocardial infarction

Full Text

References

References
1 Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1: 397-401.
2 ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected AMI. ISIS-2. Lancet 1988; 2: 349-60.
3 The GUSTO Investigators. An International randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673-82.
4 Gruppo Italiano per lo Studio della Soppravvivenza nell’ Infarto Miocardico (GISSI-2). A factorial randomised trial of Alteplase vs. Streptokinase and heparin versus no heparin among 12490 patients with acute myocardial infarction. Lancet 1990; 336: 65-71.
5 ISIS-3 (Third International Study of Infarct Survival). Collaborative Group. ISIS-3: A randomised comparison of streptokinase vs tissue plasminogen activator vs. anistreplase and of aspirin plus heparin vs. aspirin alone among 41299 cases of suspected acute myocardial infarction. Lancet 1992; 339: 753-70.
6 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.
7 Llerena L, Llerena R, Rodríguez-de la Vega A, Valdés-Rucabado JA, Fernández-Felipe R, Rodríguez-Bereau C. et al. Trombolisis intracoronaria con Estreptoquinasa Recombinante (SK-R) en el infarto agudo del miocardio. XVII Congreso Nacional de Cardiología; Guadalajara, Jalisco (México): Septiembre 29-Octubre 3 1991
8 The TIMI Study Group. The thrombolysis in myocardial infarction (TIMI) trial. Phase I findings. N Engl J Med 185 312: 932-6.
9 The GUSTO Angiographic Investigators. The effects of tissue plasminogen activators, streptokinase, or both on coronary patency, ventricular funtion, and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615-22.
10 Mainet D, del Rosario M, Toruncha A, Prats P, Valenzuela C, Lopéz Saura P. Similar, more than 6-months persisted, antibody and neutralizing with acute myocardial infarction treated with recombinant or natural streptokinase. Fibrinolysis and Proteolysis 1998; 12 (05) 301-9.
11 Clauss VA. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-46.
12 Judkins MP, Judkins EJ. The Judkins Technique. In: King III SB, Douglas Jr SJ. (eds). Coronary Arteriography. New York: Mc Graw-Hill; 1984: 182.
13 Fibrinolytic Therapy Trialists’ Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet 1994; 343: 311-22.
14 Topol EJ. Which thrombolytic agent should one choose?. Prog Cardiovasc Dis 1991; 34: 165-78.
15 Col JJ, Col-De Beys CM, Renkin JP, Lavenne-Pardonge EM, Bachy JL, Morian MH. Pharmacokinetics, Thrombolytic efficacy and hemorrhagic risk of different Streptokinase regimens in heparin- treated acute myocardial infarction. Am J Cardiol 1989; 63: 1185-92.
16 Goa KL, Henwood JM, Stolz JF, Langley MS, Clissold SP. Intravenous streptokinase. A reappraisal of its therapeutic use in acute myocardial infarction. Drugs 1990; 39: 693-719.
17 Verstraete M, Bory M, Collen D, Erbel R, Lennane RJ, Mathey D. et al. Randomised trial of recombinant tissue-type plasminogen activator versus intravenous streptokinase in myocardial infarction. Lancet 1985; 1: 842-7.
18 White HD, Norris RM, Brown MA, Takayama M, Maslowski A, Bass NM. et al. Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987; 317: 850-5.
19 Anderson JL, Sorensen SG, Moreno FL, Hackworthy RA, Browne KF, Dale HT. et al. Multicenter patency trial of intravenous Anistreplase compared with Streptokinase in myocardial infarction. Circulation 1991; 83: 126-40.