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Coagulation activity and clinical outcome in unstable coronary artery disease
1Department of Medical Sciences, Cardiology, University Hospital, Uppsala, Sweden. Jonas.Oldgren@medsci.uu.se
Insights
High levels of coagulation markers like TAT and SF in unstable coronary artery disease predict a better response to anticoagulants, reducing short-term events. However, elevated D-dimer indicates increased long-term mortality risk.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Thrombosis Research
Background:
- Unstable coronary artery disease (CAD) involves complex coagulation activation.
- Identifying patients who benefit most from anticoagulation is crucial.
- Molecular markers can reflect coagulation activity and predict outcomes.
Purpose of the Study:
- To investigate prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, soluble fibrin (SF), and D-dimer in unstable CAD patients.
- To assess the relationship between these markers and clinical events during and after anticoagulant therapy.
- To evaluate the predictive value of baseline and on-treatment marker levels for short- and long-term outcomes.
Main Methods:
- A randomized trial involving 320 unstable CAD patients.
- Patients received either inogatran or unfractionated heparin for 72 hours.
- Molecular markers of coagulation were measured at baseline, during treatment, and during follow-up.
Main Results:
- High baseline TAT or SF levels correlated with a 40% lower event rate during 30-day follow-up.
- Decreased F1+2 or TAT levels after 6 hours of treatment predicted a 50% lower 30-day event rate.
- High baseline D-dimer levels were associated with increased long-term mortality (median 29 months).
- Cardiac events clustered at treatment cessation, linked to rising TAT levels.
Conclusions:
- High baseline coagulation marker levels may identify unstable CAD patients who respond well to anticoagulants, showing reduced short-term ischemic events.
- Early benefits observed with anticoagulant therapy are diminished in long-term follow-up.
- Elevated baseline markers, particularly D-dimer, are linked to increased long-term mortality, possibly due to early reactivation of thrombosis.
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.