Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism

Cristina Gabara; Jesus Aibar; Yuji Nishimoto; Yugo Yamashita; Paolo Prandoni; Geoffrey D Barnes; Behnood Bikdeli; David Jiménez; Pablo Demelo-Rodríguez; Ma Luisa Peris; Son Truong Nguyen; Manuel Monreal; Registro Informatizado Enfermedad Trombo Embólica Investigators

doi:10.1016/j.jtha.2024.05.007

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism

J Thromb Haemost. 2024 May 16:S1538-7836(24)00289-7. doi: 10.1016/j.jtha.2024.05.007. Online ahead of print.

Collaborators

Registro Informatizado Enfermedad Trombo Embólica Investigators:
P Agudo, J Aibar, A Alberich-Conesa, A Alda-Lozano, J Alfonso, C Amado, M Angelina-García, J I Arcelus, A Ballaz, R Barba, C Barbagelata, B Barreiro, M Barrón, B Barrón-Andrés, J Bascuñana, F Beddar-Chaib, A Blanco-Molina, J C Caballero, I Cañas, G Castellanos, L Chasco, G Claver, J Criado, C De Juana-Izquierdo, J Del Toro, P Demelo-Rodríguez, M C Díaz-Pedroche, J A Díaz-Peromingo, A Dubois-Silva, J C Escribano, C Falgá, C Fernández-Aracil, C Fernández-Capitán, B Fernández-Jiménez, J L Fernández-Reyes, M A Fidalgo, I Francisco, C Gabara, F Galeano-Valle, F García-Bragado, A García-Ortega, O Gavín-Sebastián, A Gil-Díaz, C Gómez-Cuervo, A González-Munera, E Grau, L Guirado, J Gutiérrez-Guisado, L Hernández-Blasco, A Hernández-Molina, M J Hernández-Vidal, L Jara-Palomares, D Jiménez, I Jou, M D Joya, A Lalueza, R Lecumberri, P Llamas, J L Lobo, H López-Brull, M López-De la Fuente, L López-Jiménez, P López-Miguel, J J López-Núñez, A López-Ruiz, J B López-Sáez, M A Lorente, A Lorenzo, M Lumbierres, O Madridano, A Maestre, P J Marchena, M Marcos, M Martín Del Pozo, F Martín-Martos, R Martínez-Prado, J M Maza, M I Mercado, J Moisés, A Molino, M Monreal, L Monzón, M V Morales, G Muñoz-Gamito, M S Navas, J A Nieto, M J Núñez-Fernández, M Olid, L Ordieres-Ortega, M Ortiz, J Osorio, S Otálora, R Otero, N Pacheco-Gómez, J Pagán, A C Palomeque, E Paredes, P Parra-Rosado, J M Pedrajas, C Pérez-Ductor, M Pérez-Pinar, M L Peris, M L Pesce, J A Porras, R Puchades, A Rivas, F Rivera-Cívico, A Rivera-Gallego, A Rodríguez-Cobo, M Romero-Bruguera, P Ruiz-Artacho, G Salgueiro, T Sancho, V Sendín, P Sigüenza, S Soler, A Steinherr, S Suárez-Fernández, R Tirado, A Torrents-Vilar, M I Torres, J Trujillo-Santos, F Uresandi, R Valle, J F Varona, A Villalobos, P Villares, C Ay, S Nopp, I Pabinger, T Vanassche, P Verhamme, A Verstraete, H H B Yoo, A C Montenegro, S N Morales, J Roa, J Hirmerova, R Malý, F Varhaník, L Bertoletti, A Bura-Riviere, J Catella, R Chopard, F Couturaud, O Espitia, R Le Mao, B Leclerq, I Mahé, F Moustafa, L Plaisance, G Sarlon-Bartoli, P Suchon, E Versini, S Schellong, B Brenner, N Dally, G Kenet, I Tzoran, F Rashidi, P Sadeghipour, F Tahmasbi, A Abenante, G Barillari, F Bilora, D Bissacco, B Brandolin, R Casana, M Ciammaichella, D Colaizzo, F Dentali, P Di Micco, M Giorgi-Pierfranceschi, E Grandone, E Imbalzano, D Lambertenghi-Deliliers, R Martini, T Meschi, F Negro, A Poz, P Prandoni, P Simioni, C Siniscalchi, B Taflaj, A Ticinesi, A Tufano, A Visonà, B Zalunardo, P Kalnina, D Kigitovica, A Skride, M Zicans, Y Nishimoto, Y Yamashita, Z Tazi-Mezalek, S Fonseca, R Marques, J Meireles, S Pinto, M Bosevski, M Zdraveska, H Bounameaux, L Mazzolai, A Aujayeb, B Bikdeli, J A Caprini, A Khalil, J Tafur, I Weinberg, H M Bui, S T Nguyen, K Q Pham, G B Tran

Affiliations

¹ Internal Medicine Department, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
² Internal Medicine Department, Hospital Clínic de Barcelona, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. Electronic address: jaibar@clinic.cat.
³ Division of Cardiology, Osaka General Medical Center, Osaka, Japan; Cardiology Department, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan.
⁴ Cardiovascular Medicine Department, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁵ Arianna Foundation on Anticoagulation, Bologna, Italy.
⁶ Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA.
⁷ Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Thrombosis Research Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Yale New Haven Hospital (YNHH)/Yale Center for Outcomes Research and Evaluation (CORE), New Haven, Connecticut, USA; Cardiovascular Research Foundation (CRF), New York City, New York, USA.
⁸ Respiratory Department, Hospital Ramón y Cajal and Universidad de Alcalá. Madrid, CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
⁹ Department of Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
¹⁰ Department of Internal Medicine, Consorcio Hospitalario Provincial de Castellón, Castellón, Spain; Universidad Cardenal Herrera-CEU, Centro de Estudios Universitarios (CEU), Castellón, Spain.
¹¹ Department of Hematology, Cho Ray Hospital, Ho Chi Minh, Vietnam.
¹² Chair for the Study of Thromboembolic Disease, Faculty of Health Sciences, Universidad Católica San Antonio de Murcia, Murcia, Spain; Centro de Investigación Biomédica en Red (CIBER), Enfermedades Respiratorias (CIBERES), Madrid, Spain.

PMID: 38762019
DOI: 10.1016/j.jtha.2024.05.007

Abstract

Background: The duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding.

Objectives: Analyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation.

Methods: We compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding.

Results: Of 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding.

Conclusion: Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.

Keywords: bleeding; mortality; recurrence; unprovoked; venous thromboembolism.