Rationale and design of a study on D-dimer use to stratify patients after a first unprovoked venous thromboembolism for their risk of recurrence: extended low-dose Apixaban given only to patients with positive D-dimer results

Abstract

Optimal duration of anticoagulation in patients with a first venous thromboembolism (VTE) is still uncertain. Extended anticoagulant treatment beyond the first 3 to 6 months is recommended in patients with unprovoked VTE for their high risk of recurrence, provided the risk of bleeding during anticoagulation is not high. Recent meta-analyses indicated that only one-third of these patients have a recurrence 10 years after anticoagulation is stopped, whereas the risk of major bleeding is consistent and persistent during anticoagulation. We designed the prospective, multicenter Apidulcis study to test whether serial D-dimer measurements, using commercial assays with predefined sex-specific cutoffs (350 ng/mL and 500 ng/mL for men and women, respectively, for assays expressing results as fibrinogen equivalent units), may be useful to stratify patients for the risk of recurrence. Those presenting positive D-dimer results, considered at higher risk, will receive low dose Apixaban, 2.5 mg tablets BID for 18 months, whereas those with persistently negative D-dimer results, considered at lower risk, will remain without anticoagulant treatment. Outpatients with a first VTE (unprovoked or associated with weak risk factors), aged 18 to 74 years, who have already received anticoagulation for at least 12 months are eligible for the study.