Risk of post-thrombotic syndrome after subtherapeutic warfarin anticoagulation for a first unprovoked deep vein thrombosis: results from the REVERSE study

. Background: Risk factors for post-thrombotic syndrome (PTS) remain poorly understood. Objectives: In this multinational multicenter study, we evaluated whether subtherapeutic warfarin anticoagulation was associated with the development of PTS. Methods: Patients with a first unprovoked deep venous thrombosis (DVT) received standard anticoagulation for 57 months and were then assessed for PTS. The time in the therapeutic range was calculated from the international normalized ratio (INR) data. An INR below 2, more than 20% of the time, was considered as subtherapeutic anticoagulation. Results: Of the 349 patients enrolled, 97 (28%) developed PTS. The overall frequency of PTS in patients with subtherapeutic anticoagulation was 33.5%, compared with 21.6% in those with an INR below two for = 20% of the time (P = 0.01). During the first 3 months of therapy, the odds ratio (OR) for developing PTS if a patient had subtherapeutic anticoagulation was 1.78 (95% confidence interval [CI] 1.102.87). After adjusting for confounding variables, the OR was 1.84 (95% CI 1.133.01). Corresponding ORs for the full period of anticoagulation were 1.83 (95% CI 1.143.00) [crude] and 1.88 (95% CI 1.153.07) [adjusted]. Conclusion: Subtherapeutic warfarin anticoagulation after a first unprovoked DVT was significantly associated with the development of PTS.