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.

D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study / Palareti, G.; Poli, D.; Pesavento, R.; Legnani, C.; Antonucci, E.; Bucherini, E.; Testa, S.; Paoletti, O.; Chistolini, A.; Ceccato, D.; Martinelli, I.; Bucciarelli, P.; Falanga, A.; Tosetto, A.; Sarti, L.; Mastroiacovo, D.; Cosmi, B.; Visona, A.; Santoro, R. C.; Zanatta, N.; Grandone, E.; Bertu, L.; Pengo, V.; Caiano, L.; Prandoni, P.; Lotti, E.; Crudele, F.; Ageno, W.; Abenante, A.; Colombo, G.; Guarascio, M.; Cancellieri, E.; Morandini, R.; Zambelli, S.; Martini, S.; Vastola, M.; Serrao, A.; Abbattista, M.; Artoni, A.; Capecchi, M.; Gianniello, F.; Scimeca, B.; Barcella, L.; Gamba, S.; Lerede, T.; Maggioni, A.; Schieppati, F.; Russo, L.; Zunino, F.; Artuso, A.; Bellesso, S.; Cadau, J.; Carli, G.; Nichele, I.; Perbellini, O.; Caronna, A.; Gabrielli, F.; Lami, F.; Nicolini, A.; Scaglioni, F.; Pinelli, M.; Desideri, G.; Borgese, L.; Favaretto, E.; Libra, A.; Migliaccio, L.; Sartori, M.; Panzavolta, C.; Scandiuzzi, T.; Zalunardo, B. -M.; Ierardi, A.; Leotta, M.; Strangio, A.; Guzzon, S.; Colaizzo, D.; Favuzzi, G.; Lombardi, M. R.; Ferrini, P. M.; Tassoni, M. I.; Corradini, S.; Iotti, M.; Lambertini, I.; Veropalumbo, M. R.; Lessiani, G.; Parisi, R.; Bortoluzzi, C.; Vo, H. N.; Chiarugi, P.; Casini, M.; Violo, C.; Nuti, M.; Angeloni, L.; Carrozzi, L.; Pancani, R.; Chimera, D.; Conti, V.; Meschi, C.; Cattaneo, M.; Podda, G.; Birocchi, S.; Cuppini, S.; Marzolo, M.; Milan, M.; Martini, G.; Merelli, S.; Pontoglio, S.; Portesi, N.; Villalta, S.; De Lucchi, L.; Sponghiado, A.; Becattini, C.; Giustozzi, M.; Vinci, A.; Pignatelli, P.; Bucci, T.; Menichelli, D.; Pastori, D.; Pomero, F.; Casalis, S.; Galli, E.; Ciammaichella, M.; Maida, R.; De Cristofaro, R.; Alberelli, M. A.; Basso, M. R.; De Candia, E.; Di Gennaro, L.; Mumoli, N.; Capra, R.; Orlando, M.; Porta, C.; Rotiroti, G.; Demarco, M.; Petrillo, P.; Rossi, E.; Bartolomei, F.; Soldati, D.; Russo, U.; Burgo, I.; Ziliotti, M.; Pataccini, C.; Terroni, L.; Ugolotti, M. C.; Di Giorgio, A.; Cavagna, L.; Mete, F.; Gino, M.; Santoro, A.; De Carlo, A.; Cappelli, R.; Bicchi, M.; Dyrmo, L.; Grifoni, E.; Masotti, L.; Ria, L.; Spagnolo, M.; Rupoli, S.; Federici, I.; Morsia, E.; Scortechini, A. R.; Torre, E.; Franchini, M.; Montorsi, P.; Galgano, G.; De Luca, A.; Muiesan, M. L.; Paini, A.; Stassaldi, D.; Denas, G.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 6:23(2022), pp. 6005-6015. [10.1182/bloodadvances.2022007973]

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

Caronna A.
Membro del Collaboration Group
;
Gabrielli F.
Membro del Collaboration Group
;
Lami F.
Membro del Collaboration Group
;
Nicolini A.
Membro del Collaboration Group
;
Scaglioni F.
Membro del Collaboration Group
;
2022

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.
2022
6
23
6005
6015
D-dimer and reduced-dose apixaban for extended treatment after unprovoked venous thromboembolism: the Apidulcis study / Palareti, G.; Poli, D.; Pesavento, R.; Legnani, C.; Antonucci, E.; Bucherini, E.; Testa, S.; Paoletti, O.; Chistolini, A.; Ceccato, D.; Martinelli, I.; Bucciarelli, P.; Falanga, A.; Tosetto, A.; Sarti, L.; Mastroiacovo, D.; Cosmi, B.; Visona, A.; Santoro, R. C.; Zanatta, N.; Grandone, E.; Bertu, L.; Pengo, V.; Caiano, L.; Prandoni, P.; Lotti, E.; Crudele, F.; Ageno, W.; Abenante, A.; Colombo, G.; Guarascio, M.; Cancellieri, E.; Morandini, R.; Zambelli, S.; Martini, S.; Vastola, M.; Serrao, A.; Abbattista, M.; Artoni, A.; Capecchi, M.; Gianniello, F.; Scimeca, B.; Barcella, L.; Gamba, S.; Lerede, T.; Maggioni, A.; Schieppati, F.; Russo, L.; Zunino, F.; Artuso, A.; Bellesso, S.; Cadau, J.; Carli, G.; Nichele, I.; Perbellini, O.; Caronna, A.; Gabrielli, F.; Lami, F.; Nicolini, A.; Scaglioni, F.; Pinelli, M.; Desideri, G.; Borgese, L.; Favaretto, E.; Libra, A.; Migliaccio, L.; Sartori, M.; Panzavolta, C.; Scandiuzzi, T.; Zalunardo, B. -M.; Ierardi, A.; Leotta, M.; Strangio, A.; Guzzon, S.; Colaizzo, D.; Favuzzi, G.; Lombardi, M. R.; Ferrini, P. M.; Tassoni, M. I.; Corradini, S.; Iotti, M.; Lambertini, I.; Veropalumbo, M. R.; Lessiani, G.; Parisi, R.; Bortoluzzi, C.; Vo, H. N.; Chiarugi, P.; Casini, M.; Violo, C.; Nuti, M.; Angeloni, L.; Carrozzi, L.; Pancani, R.; Chimera, D.; Conti, V.; Meschi, C.; Cattaneo, M.; Podda, G.; Birocchi, S.; Cuppini, S.; Marzolo, M.; Milan, M.; Martini, G.; Merelli, S.; Pontoglio, S.; Portesi, N.; Villalta, S.; De Lucchi, L.; Sponghiado, A.; Becattini, C.; Giustozzi, M.; Vinci, A.; Pignatelli, P.; Bucci, T.; Menichelli, D.; Pastori, D.; Pomero, F.; Casalis, S.; Galli, E.; Ciammaichella, M.; Maida, R.; De Cristofaro, R.; Alberelli, M. A.; Basso, M. R.; De Candia, E.; Di Gennaro, L.; Mumoli, N.; Capra, R.; Orlando, M.; Porta, C.; Rotiroti, G.; Demarco, M.; Petrillo, P.; Rossi, E.; Bartolomei, F.; Soldati, D.; Russo, U.; Burgo, I.; Ziliotti, M.; Pataccini, C.; Terroni, L.; Ugolotti, M. C.; Di Giorgio, A.; Cavagna, L.; Mete, F.; Gino, M.; Santoro, A.; De Carlo, A.; Cappelli, R.; Bicchi, M.; Dyrmo, L.; Grifoni, E.; Masotti, L.; Ria, L.; Spagnolo, M.; Rupoli, S.; Federici, I.; Morsia, E.; Scortechini, A. R.; Torre, E.; Franchini, M.; Montorsi, P.; Galgano, G.; De Luca, A.; Muiesan, M. L.; Paini, A.; Stassaldi, D.; Denas, G.. - In: BLOOD ADVANCES. - ISSN 2473-9529. - 6:23(2022), pp. 6005-6015. [10.1182/bloodadvances.2022007973]
Palareti, G.; Poli, D.; Pesavento, R.; Legnani, C.; Antonucci, E.; Bucherini, E.; Testa, S.; Paoletti, O.; Chistolini, A.; Ceccato, D.; Martinelli, I....espandi
File in questo prodotto:
File Dimensione Formato  
blooda_adv-2022-007973-main.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 363.84 kB
Formato Adobe PDF
363.84 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1366271
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 14
social impact