The hemostatic effects of warfarin titration in post CABG patients in comparison to placebo treatment.
BACKGROUND
Since coronary artery bypass graft patients remain at risk of coronary artery and bypass graft occlusion after successful surgery, adjunct treatment regimens are under investigation. In a study of the patients of the multicenter Post Coronary Artery Bypass Graft (Post CABG) Trial, 1 mg warfarin was found to have no important effect on coagulation parameters.


METHODS
The effects of 1, 2 and 3 mg warfarin were evaluated at six-week intervals in 20 Post CABG Trial patients receiving titrated dose increases in comparison to 20 patients of similar age, gender and time from CABG treated with placebo.


RESULTS
International normalized ratio (INR) values increased with warfarin dose increments for 1, 2, and 3 mg, respectively (0.95+/-0.16, 1.08+/-0.19, and 1.34+/-0.39) and in comparison to placebo treated patients (dosextreatment p<0.001). Factor VII coagulant activity decreased with warfarin titration (1 mg, 119.0+/-18.3 %; 2 mg, 100.6+/-32.8 %; 3 mg, 95.0+/-27.8 %) and in comparison to placebo (dosextreatment p=0.008). Levels of prothrombin fragment F1.2, tissue plasminogen activator, fibrinogen and von Willebrand factor were unchanged with warfarin dose increments and in comparison to placebo.


CONCLUSIONS
At doses up to 3 mg, warfarin acts on the INR through a reduction of factor VII with no effect on the fibrinolytic system, fibrinogen or von Willebrand factor. At these doses F1.2 did not document reduced coagulation activity. The observations of this study were consistent with the decision in the Post CABG Trial to increase the warfarin dose above 1 mg to achieve a distinct effect of warfarin that was less than full anticoagulation.
Walenga
J M
JM
Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153, USA. jwaleng@lumc.edu
Hoppensteadt
D
D
Pifarré
R
R
Fox
N L
NL
Forman
S
S
Hunninghake
D B
DB
Campeau
L
L
Herd
J A
JA
Hoogwerf
B J
BJ
Hickey
A
A
Probstfield
J L
JL
Terrin
M L
ML
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000097:blood / Q000517:prevention & control* / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005167:Factor VII / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D011183:Postoperative Complications / Q000517:prevention & control*; D019106:Postoperative Hemorrhage / Q000139:chemically induced; D011516:Prothrombin / Q000032:analysis; D012008:Recurrence; D012501:Saphenous Vein / Q000473:pathology / Q000637:transplantation; D013927:Thrombosis / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000032:analysis; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000032:analysis
D000925:Anticoagulants; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D014841:von Willebrand Factor; D014859:Warfarin; D005167:Factor VII; D011516:Prothrombin; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D001241:Aspirin