Early versus delayed introduction of oral vitamin K antagonists in combination with low-molecular-weight heparin in the treatment of deep vein thrombosis - A randomized clinical trial

Objective: To compare oral anticoagulant treatment (fluindione) started on either the Ist or the 10th day of a low-molecular-weight heparin (enoxapari n) treatment for deep vein thrombosis confirmed by venography. Design: An o pen, multicenter, randomized study in two parallel treatment groups. Interv entions: All patients received enoxaparin, 1 mg/kg s.c. twice daily, and or al fluindione, 20 mg once daily, either beginning on day 1 or on day 10 of the enoxaparin treatment. Enoxaparin was discontinued once the internationa l normalized ratio under fluindione was stable between 2.0 and 3.0 over 2 d ays. Fluindione treatment was maintained during a 3-month follow-up period. Outcome Measurements: Specific examinations (venography and/or V/Q lung sc anning and/or angiography) were performed only in the event of a clinically suspected recurrence of venous thromboembolism during the 3-month follow-u p period. All cases were blindly assessed by an independent Reading Committ ee. Results: A clinically suspected venous thromboembolism was confirmed by objective tests in 1 of 223 patients (group of delayed introduction of flu indione; n = 111). Equivalence was demonstrated between the two treatment s chedules (p < 0.0001) for a maximal difference of 10% (90% confidence inter val: -2.42 to 0.58). The mean duration of hospitalization was significantly reduced (p = 0.0001) in the group with early introduction of fluindione. T he incidence of hemorrhage was comparable between the two treatment groups. Conclusion: Early and delayed introduction of oral anticoagulant treatment in association with subcutaneous enoxaparin in patients with deep vein thr ombosis was shown to be equivalent in preventing the recurrence of venous t hromboembolism. In patients with early introduction of oral anticoagulant, hospitalization was significantly reduced.