Inflammation and Coagulation Activity in Unstable Coronary Artery Disease and the Influences of Thrombin Inhibition

Abstract: In patients with unstable coronary artery disease, this study evaluated the degree of inflammation and coagulation activity, relations to myocardial cell damage, prognosis, and influences of randomisation to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor (n=904), or unfractionated heparin (n=305). Anticoagulant treatment effects were evaluated with aPT time. In inogatran treated patients with aPT times ? 44 s (median), the 7-days event rate - death, myocardial infarction or refractory angina – was 11.6 %, compared to 6.6 % with aPT times < 44 s (p=0.01). Higher aPT times was related to improved outcome during heparin treatment.Markers of inflammation, i.e. fibrinogen and C-reactive protein (CRP), and coagulation, i.e. prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), soluble fibrin (SF) and D-dimer were analysed in serial samples (n=320). High fibrinogen, F1+2 and D-dimer levels persisted at 30 days. Patients with myocardial damage, detected by elevated troponin, had higher levels of all markers except TAT.Ischemic events occurred at 30 days in 17 % of patients with high (pre-treatment top tertile) and 8.5 % of patients with lower fibrinogen levels (p=0.03), while high CRP levels only were related to increased mortality. At 30 days, patients with high compared to low pre-treatment levels of TAT or SF had 40 % lower event rate. Patients with early decreased compared to raised F1+2 or TAT levels during treatment had 50 % lower 30-days event rate (p<0.05). Conclusions: The aPT time is an inappropriate indicator of antithrombotic efficacy. The raise in fibrinogen in the acute phase is sustained, and indicates risk of thrombosis and new ischemic events. The pronounced CRP elevation is transient, but associated with increased mortality. Higher coagulation activity may identify patients with a thrombotic condition as the major cause of instability, who are best responders to anticoagulant therapy. However, reactivation of coagulation activity with raised risk of ischemic events is a concern at cessation of treatment.