D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study

Gualtiero Palareti, Daniela Poli, Raffaele Pesavento, Cristina Legnani, Emilia Antonucci, Eugenio Bucherini, Sophie Testa, Oriana Paoletti, Antonio Chistolini, Davide Ceccato, Ida Martinelli, Paolo Bucciarelli, Anna Falanga, Alberto Tosetto, Luca Sarti, Daniela Mastroiacovo, Benilde Cosmi, Adriana Visonà, Rita Carlotta Santoro, Nello ZanattaElvira Grandone, Lorenza Bertù, Vittorio Pengo, Lucia Caiano, Paolo Prandoni, Elena Lotti, Felice Crudele, Walter Ageno, Alessia Abenante, Giovanna Colombo, Matteo Guarascio, Emilia Cancellieri, Rossella Morandini, Silvia Zambelli, Sauro Martini, Monica Vastola, Alessandra Serrao, Maria Abbattista, Andrea Artoni, Marco Capecchi, Francesca Gianniello, Barbara Scimeca, Luca Barcella, Sara Gamba, Teresa Lerede, Anna Maggioni, Francesca Schieppati, Laura Russo, Federica Zunino, Anna Artuso, Stefania Bellesso, Jessica Cadau, Giuseppe Carli, Ilaria Nichele, Omar Perbellini, Antonella Caronna, Filippo Gabrielli, Francesca Lami, Alberto Nicolini, Federica Scaglioni, Mauro Pinelli, Giovambattista Desideri, Laura Borgese, Elisabetta Favaretto, Alessia Libra, Ludovica Migliaccio, Michelangelo Sartori, Chiara Panzavolta, Tatiana Scandiuzzi, Benia-Mino Zalunardo, Antonella Ierardi, Marzia Leotta, Alessandra Strangio, Samuele Guzzon, Donatella Colaizzo, Giovanni Favuzzi, Maria Rosa Lombardi, Piera Maria Ferrini, Maria Ilaria Tassoni, Sara Corradini, Matteo Iotti, Isabella Lambertini, Maria Rosaria Veropalumbo, Gianfranco Lessiani, Roberto Parisi, Cristiano Bortoluzzi, Hong Ngoc Vo, Paolo Chiarugi, Monica Casini, Caterina Violo, Marco Nuti, Lucia Angeloni, Laura Carrozzi, Roberta Pancani, Davide Chimera, Valentina Conti, Claudia Meschi, Marco Cattaneo, Gianmarco Podda, Simone Birocchi, Stefano Cuppini, Marco Marzolo, Marta Milan, Giuliana Martini, Sara Merelli, Sara Pontoglio, Nicola Portesi, Sabina Villalta, Lara De Lucchi, Alessandra Sponghiado, Cecilia Becattini, Michela Giustozzi, Alessandra Vinci, Pasquale Pignatelli, Tommaso Bucci, Danilo Menichelli, Daniele Pastori, Fulvio Pomero, Sara Casalis, Eleonora Galli, Maurizio Ciammaichella, Rosa Maida, Raimondo De Cristofaro, Maria Adele Alberelli, Maria Rosaria Basso, Erica De Candia, Leonardo Di Gennaro, Nicola Mumoli, Riccardo Capra, Mariantonia Orlando, Cesare Porta, Giuseppe Rotiroti, Monica Demarco, Paola Petrillo, Elena Rossi, Francesca Bartolomei, Denise Soldati, Umberto Russo, Ilaria Burgo, Maurizio Ziliotti, Corrado Pataccini, Lorenza Terroni, Maria Chiara Ugolotti, Angela Di Giorgio, Laura Cavagna, Francesca Mete, Miriam Gino, Angelo Santoro, Armando De Carlo, Roberto Cappelli, Maurizio Bicchi, Lediona Dyrmo, Elisa Grifoni, Luca Masotti, Luigi Ria, Marina Spagnolo, Serena Rupoli, Irene Federici, Erika Morsia, Anna Rita Scortechini, Elena Torre, Massimo Franchini, Paolo Montorsi, Giuseppe Galgano, Anna De Luca, Maria Lorenza Muiesan, Anna Paini, Deborah Stassaldi, Gentian Denas

Research output: Contribution to journalArticle

Abstract

D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 [39.1%]) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval [CI], 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio [HR], 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.
Original languageEnglish
Pages (from-to)6005-6015
Number of pages11
JournalBlood advances
Volume6
DOIs
Publication statusPublished - 2022

Keywords

  • venous thromboembolism, d-dimer, anticoagulation therapy, apixaban

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