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.

STUDY DESIGN

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.