Effects of warfarin on markers of hypercoagulability in patients with heart failure

• Published in: The American heart journal 1997-07, Vol.134 (1), p.27-36
• Main Authors: Jafri, Syed M., Mammen, Eberhard F., Masura, Julie, Goldstein, Sidney
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Antifibrinolytic Agents - blood; Antithrombin III - analysis; Biological and medical sciences; Biomarkers - blood; Blood Coagulation - drug effects; Cardiac Output, Low - blood; Cardiac Output, Low - complications; Cardiology. Vascular system; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products - analysis; Fibrinolysin - analysis; Follow-Up Studies; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hemostasis - drug effects; Humans; Male; Medical sciences; Middle Aged; Peptide Fragments - analysis; Peptide Hydrolases - analysis; Placebos; Protein Precursors - analysis; Prothrombin - analysis; Thrombin - analysis; Thrombosis - blood; Thrombosis - prevention & control; Warfarin - administration & dosage; Warfarin - therapeutic use
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/S0002-8703(97)70103-0

Heart failure is associated with a hypercoagulable state. A single-center, randomized, double-blind, placebo-controlled trial was performed to test the hypothesis that warfarin will modify a hypercoagulable state in heart failure. This study included 76 patients with heart failure. At baseline, patients had evidence for a hypercoagulable state with elevated plasma levels of thrombin/antithrombin III (TAT) complexes (3.4 ± 2.0 ng/ml), prothrombin fragment F1 + 2 (1.5 ± 0.9 nmol/L), and D-dimers (630 ± 401 ng/ml). Warfarin therapy (international normalized ratio [INR] 2.7 ± 1.3) significantly decreased plasma levels of TAT complexes ( p < 0.002), F1 + 2 ( p < 0.001), and D-dimers ( p < 0.001) when compared with baseline values at 1, 2, and 3 months of therapy. In contrast, patients receiving placebo had persistent elevation of TAT complexes ( p = not significant [NS]), F1 + 2 ( p = NS), and D-dimers ( p = NS) during follow-up at 1, 2, and 3 months. The two treatment groups followed different trends over time for all three markers ( p < 0.001). The effect of low-intensity warfarin (INR 1.3 ± 0.08) versus moderate-intensity warfarin (INR 2.3 ± 1.1) on markers of hypercoagulability was evaluated in 14 patients. When compared with baseline, low-intensity warfarin administration decreased plasma levels of TAT complexes ( p = NS), F1 + 2 ( p = 0.05), and D-dimers ( p = 0.04). In these patients F1 + 2 was further reduced with moderate-intensity warfarin ( p < 0.001). Our findings suggest that a hypercoagulable state in heart failure can be modified by warfarin therapy. (Am Heart J 1997;134: 27-36.)