Activation of the inflammation, coagulation, and fibrinolysis systems, without influence of abciximab infusion in patients with non-ST-elevation acute coronary syndromes treated with dalteparin: A GUSTO IV substudy
BACKGROUND: In acute coronary syndromes, the inflammation and the coagulation systems are activated, implying an impaired outcome. In addition to platelet inhibition, recent evidence suggests that the glycoprotein IIb/IIIa receptor inhibitor abciximab attenuates inflammation and coagulation activity. METHODS: The Swedish Global Utilization of Strategies To open Occluded arteries-IV (GUSTO-IV) substudy included 404 patients with non-ST-elevation acute coronary syndromes. In addition to aspirin and dalteparin, all patients were randomized to receive abciximab infusion for 24 hours or 48 hours or corresponding placebo without early coronary revascularization. Plasma samples were obtained at baseline and 24, 48, and 72 hours. RESULTS: The median levels of the coagulation markers thrombin/antithrombin complex and soluble fibrin increased significantly from 3.1 to 3.7 ug/L (baseline to peak; P <.001) and from 20 to 23 nmol/L (P <.001), respectively. The fibrinolysis marker, tissue plasminogen-activator, also increased its median levels, from 11.7 to 17.5 ug/L (P <.001), whereas the median level of plasminogen-activator-inhibitor was unchanged. The inflammatory markers interleukin-6, C-reactive protein, and fibrinogen also increased their median levels (5.4-7.8 ng/L, P <.001; 4.4-8.7 mg/L, P <.001; 3.3-3.9 g/L, P <.001). However, there were no differences in median levels or in changes of median levels of any marker at any point between the placebo group and any of the abciximab groups. CONCLUSIONS: In non-ST-elevation acute coronary syndrome, there was a simultaneous activation of the inflammation, coagulation, and fibrinolysis systems, despite aspirin and dalteparin treatment. Prolonged treatment with abciximab had no influence of the activation of these systems.
|Keywords||*Inflammation, 0 (Antibodies, Monoclonal), 0 (Anticoagulants), 0 (Biological Markers), 0 (Blood Coagulation Factors), 0 (Immunoglobulins, Fab), 0 (Interleukin-6), 0 (Platelet Aggregation Inhibitors), 0 (Tedelparin), 143653-53-6 (abciximab), 9001-31-4 (Fibrin), 9007-41-4 (C-Reactive Protein), Aged, Angina, Unstable/blood/*drug therapy, Antibodies, Monoclonal/pharmacology/*therapeutic use, Anticoagulants/pharmacology/*therapeutic use, Biological Markers/blood, Blood Coagulation Factors/analysis, Blood Coagulation/*drug effects, C-Reactive Protein/analysis, Double-Blind Method, Electrocardiography, Female, Fibrin/analysis, Fibrinolysis/drug effects, Human, Immunoglobulins, Fab/pharmacology/*therapeutic use, Interleukin-6/blood, Male, Middle Aged, Platelet Aggregation Inhibitors/pharmacology/*therapeutic use, Support, Non-U.S. Gov't, Tedelparin/pharmacology/*therapeutic use|
|Persistent URL||dx.doi.org/10.1016/j.ahj.2003.09.014, hdl.handle.net/1765/5720|
James, S.K., Siegbahn, A., Califf, R.M., Simoons, M.L., Wallentin, L.C., Armstrong, P.W., & Barnathan, E.S.. (2004). Activation of the inflammation, coagulation, and fibrinolysis systems, without influence of abciximab infusion in patients with non-ST-elevation acute coronary syndromes treated with dalteparin: A GUSTO IV substudy. American Heart Journal, 147(2), 267–274. doi:10.1016/j.ahj.2003.09.014