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

The Apidulcis study


Submitted: 22 December 2021
Accepted: 9 February 2022
Published: 22 March 2022
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Authors

  • Gualtiero Palareti Arianna Anticoagulazione Foundation, Bologna, Italy.
  • Paolo Prandoni Arianna Anticoagulazione Foundation, Bologna, Italy.
  • Cristina Legnani Arianna Anticoagulazione Foundation, Bologna, Italy.
  • Emilia Antonucci Arianna Anticoagulazione Foundation, Bologna, Italy.
  • Serena Zorzi Arianna Anticoagulazione Foundation, Bologna, Italy.
  • Alberto Tosetto Department of Hematology, Center for Hemorrhagic and Thrombotic Diseases, AULSS8 Berica, Vicenza, Italy.
  • Lorenza Bertù Research Center on Thromboembolic Diseases and Antithrombotic Therapies, University of Insubria, Varese, Italy.
  • Sophie Testa Department of Laboratory Medicine, Haemostasis and Thrombosis Center, AO Istituti Ospitalieri, Cremona, Italy.
  • Vittorio Pengo Thrombosis Research Laboratory, Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Italy.
  • Walter Ageno Department of Medicine and Surgery, University of Insubria, Varese, Italy.
  • Ida Martinelli A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milano, Italy.
  • Benilde Cosmi Simple Departmental Structure - Angiology and Coagulation Diseases, IRCCS Bologna University Hospital, Università di Bologna, Italy.
  • Eugenio Bucherini Simple Departmental Structure - Vascular Medicine and Angiology, Ospedale Civile Faenza, Faenza (RA), Italy.
  • Daniela Poli Thrombosis Center, Careggi Hospital, Florence, Italy.

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.


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Palareti, G. ., Prandoni, P. ., Legnani, C. ., Antonucci, E. ., Zorzi, S. ., Tosetto, A. ., Bertù, L. ., Testa, S. ., Pengo, V. ., Ageno, W. ., Martinelli, I. ., Cosmi, B. ., Bucherini, E. ., & Poli, D. . (2022). 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: The Apidulcis study. Bleeding, Thrombosis, and Vascular Biology, 1(1). https://doi.org/10.4081/btvb.2022.10

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