Effects of warfarin on markers of hypercoagulability in patients with heart failure.
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.
Jafri
S M
SM
Henry Ford Hospital, Heart & Vascular Institute, Detroit, Mich. 48202, USA.
Mammen
E F
EF
Masura
J
J
Goldstein
S
S
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000097:blood; D000990:Antithrombin III / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D002303:Cardiac Output, Low / Q000097:blood / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis; D005500:Follow-Up Studies; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D010919:Placebos; D011498:Protein Precursors / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D013917:Thrombin / Q000032:analysis; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D010919:Placebos; D011498:Protein Precursors; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D014859:Warfarin; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D013917:Thrombin; D005341:Fibrinolysin