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 c oronary 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 w arfarin 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-w eek intervals in 20 Post CABG Trial patients receiving titrated dose increa ses in comparison to 20 patients of similar age, gender and time from CABG treated with placebo. Results: International normalized ratio (INR) values increased with warfari n 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 (dosex treatment 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 +/- 2 7.8 %) and in comparison to placebo (dosextreatment p=0.008). Levels of pro thrombin fragment F1.2, tissue plasminogen activator, fibrinogen and von Wi llebrand factor were unchanged with warfarin dose increments and in compari son to placebo. Conclusions: At doses up to 3 mg, warfarin acts on the INR through a reduct ion of factor VII with no effect on the fibrinolytic system, fibrinogen or von Willebrand factor. At these doses F1.2 did not document reduced coagula tion activity. The observations of this study were consistent with the deci sion in the Post CABG Trial to increase the warfarin dose above 1 mg to ach ieve a distinct effect of warfarin that was less than full anticoagulation.