Level 1: Likely reliable evidence
A randomized trial evaluated the efficacy of extended anticoagulation in 608 patients aged 18-85 years with first episodes of symptomatic, unprovoked venous thromboembolism (deep venous thrombosis and/or pulmonary embolism) who completed at least three months of oral anticoagulation (warfarin or acenocoumarol to a target international normalized ratio of 2-3) (N Engl J Med. 2006;355:1780-1789). All patients underwent D-dimer testing one month after stopping anticoagulation, and 223 (37%) with abnormal D-dimer assay were randomized to resume or discontinue anticoagulation. Eleven additional patients with lupus anticoagulant, elevated antiphospholipid antibody, or antithrombin deficiency were excluded from the trial. The remaining participants were followed for a mean 1.4 years (range 9-18 months). Comparing those who resumed vs. those who discontinued anticoagulation, 2.9% vs. 15% had recurrent thromboembolism (P =.02, NNT 9); the rate was 2 vs. 10.9 per 100 patient-years (NNT 11.2 patient-years). Also reported were episodes of major bleeding (1 vs. 0) and death (1 vs. 1). In patients with a normal D-dimer assay, 385 (63%) remained off anticoagulation and 14 resumed anticoagulation for clinical conditions.
Twenty-four (6.2%) patients with normal D-dimer who discontinued anticoagulation had a recurrent thromboembolism.