Eduardo Ramacciotti, Leandro Barile Agati, Daniela Calderaro, Valéria Cristina Resende Aguiar, Alex C Spyropoulos, Caroline Candida Carvalho de Oliveira, Jessica Lins dos Santos, Giuliano Giova Volpiani, Marcone Lima Sobreira, Edwaldo Edner Joviliano, Milton Sérgio Bohatch Júnior, Benedito Antônio Lopes da Fonseca, Maurício Serra Ribeiro, Cesar Dusilek, Kengi Itinose, Suzanna Maria Viana Sanches, Karine de Almeida Araujo Ramos, Nara Franzin de Moraes, Paulo Fernando Guimarães Morando Marzocchi Tierno, André Luiz Malavasi Longo de Oliveira, Adriano Tachibana, Rodrigo Caruso Chate, Marcus Vinícius Barbosa Santos, Bruno Bezerra de Menezes Cavalcante, Ricardo Cesar Rocha Moreira, Chiann Chang, Alfonso Tafur, Jawed Fareed, Renato D Lopes, Tania Benevenuto Caltabiano, Breno Hattori, Marcello da Silva Jardim, Igor Marinho, Ivan Silva Marinho, Liane Mara Melo Batista, Lucas Rivabem, Carlos Alberto Kenji Nakashima, Ana Carla Gois Franco, Renata Fernanda de Oliveira Pereira, Giana Caroline Strack Neves, Izara de Castro e Souza, Bruno Moraes Ribas, Flavia Ramos Tristão, Marcus Vinicius Barbosa Santos, Science Valley Research Institute, Santo André, Universidade de São Paulo (USP), Zucker School of Medicine at Hofstra/Northwell and the Feinstein Institutes for Medical Research, I M Sechenov First Moscow State Medical University, Universidade Estadual Paulista (UNESP), Hospital do Rocio, Salvador, Hospital Municipal de Barueri, São Paulo State Public Women's Health Reference Center, Hospital Israelita Albert Einstein, Institute of Teaching and Research Hapvida, Hospital Nossa Senhora das Graças, Northshore University Health System, Hemostasis and Thrombosis Research Laboratories at Loyola University Medical Center, and Duke University School of Medicine
Made available in DSpace on 2022-04-29T08:46:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Background: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. Methods: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2–3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. Findings: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2–3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12–0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. Interpretation: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. Funding: Bayer. Science Valley Research Institute Hospital e Maternidade Christóvão da Gama Grupo Leforte Santo André Unidade de Medicina Interdisciplinar em Cardiologia Instituto do Coração Hospital das Clínicas HCFMUSP Faculdade de Medicina Universidade de São Paulo Zucker School of Medicine at Hofstra/Northwell and the Feinstein Institutes for Medical Research Department of Obstetrics and Gynecology I M Sechenov First Moscow State Medical University Universidade Estadual Paulista Hospital das Clínicas de Ribeirão Preto São Paulo University Medical School Ribeirão Preto Hospital do Rocio, Campo Largo Instituto Couto Maia Salvador Hospital Municipal de Barueri São Paulo State Public Women's Health Reference Center Hospital Israelita Albert Einstein Instituto do Coração Hospital das Clínicas HCFMUSP Faculdade de Medicina Universidade de São Paulo Institute of Teaching and Research Hapvida Hospital Nossa Senhora das Graças Department of Statistics Institute of Mathematics and Statistics University of São Paulo Northshore University Health System Hemostasis and Thrombosis Research Laboratories at Loyola University Medical Center Duke Clinical Research Institute Duke University School of Medicine Universidade Estadual Paulista