Coagulation, inflammation and myocardial dysfunction in unstable coronary artery disease and the influence of glycoprotein IIb/IIIa inhibition and low molecular weight heparin

Abstract

Patients with unstable coronary artery disease (CAD) have an increased risk of subsequent myocardial infarction and death. This study evaluated the safety and efficacy of treatment with glycoprotein IIb/IIIa inhibition in addition to aspirin, low molecular- weight heparin and its influence on coagulation and inflammation. Also, early and differentiated risk assessment utilising markers of inflammation, myocardial damage and dysfunction were evaluated.

The Global Utilisation of Strategies To open Occluded arteries-IV (GUSTO-IV) trial randomised 7800 patients with unstable CAD to 24 or 48 hours infusion of abciximab or placebo in addition to routine treatment with aspirin and heparin or dalteparin. Baseline levels of creatinine, C-reactive protein (CRP), troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analysed. At selected sites, all patients received subcutaneous dalteparin (n=974), in stead of heparin infusion (n=6826). In a sub-population of dalteparin treated patients (n=404), serial measurements of markers of coagulation, fibrinolysis and inflammation were also performed. Addition of abciximab to dalteparin as the primary treatment of unstable CAD was not associated with any significant reduction in cardiac events but a doubled risk of bleedings. The combination of abciximab with dalteparin seemed as safe when used with heparin. Despite full dose dalteparin and aspirin there was a simultaneous activation of the inflammation, coagulation and fibrinolysis systems without any influence of the abciximab treatment. Elevated levels of CRP, TnT, and NT-proBNP and reduced creatinine clearance were independently related to short and long-term mortality. The best prediction of high and low risk was provided by a combination of NT-proBNP and creatinine clearance. Any detectable elevation of TnT and reduced creatinine clearance, but neither elevation of CRP nor NT-proBNP, were also independently associated to a raised risk of subsequent myocardial infarction.

Abbreviations: Acute coronary syndrome (ACS), Brain natriuretic peptide (BNP), Coefficient of variance

(CV), Coronary artery disease (CAD), Coronary artery bypass grafting (CABG), Creatine kinase-

MB (CK-MB), C-reactive protein (CRP), Electrocardiogram (ECG), Glycoprotein IIb/IIIa (GP

IIb/IIIa), Global Utilisation of Strategies To Open Occluded Arteries IV (GUSTO-IV), Interleukin-6

(Il-6), Low-molecular weight heparin (LMWH), N-terminal pro-Brain natriuretic peptide (NT-proBNP),

Myocardial infarction (MI), Percutaneous coronary intervention (PCI), Plasminogen activator

(tPA), Plasminogen activator inhibitor (PAI-1), Soluble fibrin (SF), Thrombin-antithrombin complex

(TAT), Troponin T (TnT), Unfractionated heparin (UFH).