title: Coagulation activity and clinical outcome in unstable coronary artery disease.
abstract: In the current study, we investigated molecular markers of coagulation activity, ie, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, soluble fibrin (SF), and D-dimer, and their relation to death, myocardial infarction, and refractory angina during and after anticoagulant treatment in unstable coronary artery disease. Patients with unstable coronary artery disease (N=320) were randomized to a 72-hour infusion with either inogatran, a low-molecular-mass direct thrombin inhibitor, or unfractionated heparin. During the 30-day follow-up, a 40% lower event rate was seen in patients with high compared with low baseline levels of TAT or SF. High baseline levels of coagulation activity were correlated with a larger decrease during treatment. Patients with decreased compared with raised F1+2 or TAT levels after 6 hours of treatment had a 50% lower event rate at 30 days (F1+2, P=0.04; TAT, P=0.02). At the cessation of antithrombin treatment, there was a clustering of cardiac events that tended to be related to a rise in the levels of TAT and the other markers. During long-term follow-up (median, 29 months), there was a relation between higher baseline levels of D-dimer (P=0.003) and increased mortality. High baseline levels of molecular markers of coagulation activity might identify patients with a thrombotic condition (as the major cause of instability) who are good responders to anticoagulant therapy, with a larger decrease in coagulation activity during treatment and a decreased risk of ischemic events. However, this early benefit is lost during long-term follow-up when high baseline levels of coagulation activity are associated with a raised risk of early reactivation and increased mortality.
authors.affiliation: Department of Medical Sciences, Cardiology, University Hospital, Uppsala, Sweden. Jonas.Oldgren@medsci.uu.se
authors.forename: J
authors.initials: J
authors.lastname: Oldgren
authors.forename: R
authors.initials: R
authors.lastname: Linder
authors.forename: L
authors.initials: L
authors.lastname: Grip
authors.forename: A
authors.initials: A
authors.lastname: Siegbahn
authors.forename: L
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D000925:Anticoagulants / Q000627:therapeutic use; D000990:Antithrombin III / Q000032:analysis; D000991:Antithrombins / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D001777:Blood Coagulation / Q000187:drug effects*; D005260:Female; D005337:Fibrin / Q000032:analysis; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005500:Follow-Up Studies; D005998:Glycine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D010880:Piperidines / Q000627:therapeutic use; D011516:Prothrombin / Q000032:analysis; D011897:Random Allocation; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D010880:Piperidines; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; C099871:inogatran; D000990:Antithrombin III; D011516:Prothrombin; D005337:Fibrin; D006493:Heparin; D010447:Peptide Hydrolases; D005998:Glycine