Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery.
Administration, Oral
Adult
Anticoagulants
/ adverse effects
Double-Blind Method
Enoxaparin
/ adverse effects
Female
Hemorrhage
/ chemically induced
Humans
Injections, Subcutaneous
Lower Extremity
/ surgery
Male
Middle Aged
Orthopedic Procedures
Postoperative Complications
/ prevention & control
Pulmonary Embolism
/ prevention & control
Rivaroxaban
/ adverse effects
Venous Thromboembolism
/ mortality
Venous Thrombosis
/ prevention & control
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
14 05 2020
14 05 2020
Historique:
pubmed:
31
3
2020
medline:
23
5
2020
entrez:
31
3
2020
Statut:
ppublish
Résumé
Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients. In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding. A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P<0.001 for noninferiority; P = 0.01 for superiority). The incidence of bleeding did not differ significantly between the rivaroxaban group and the enoxaparin group (1.1% and 1.0%, respectively, for major bleeding or nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding). Rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilization after nonmajor orthopedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.).
Sections du résumé
BACKGROUND
Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients.
METHODS
In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding.
RESULTS
A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P<0.001 for noninferiority; P = 0.01 for superiority). The incidence of bleeding did not differ significantly between the rivaroxaban group and the enoxaparin group (1.1% and 1.0%, respectively, for major bleeding or nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding).
CONCLUSIONS
Rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilization after nonmajor orthopedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.).
Identifiants
pubmed: 32223113
doi: 10.1056/NEJMoa1913808
doi:
Substances chimiques
Anticoagulants
0
Enoxaparin
0
Rivaroxaban
9NDF7JZ4M3
Banques de données
ClinicalTrials.gov
['NCT02401594']
Types de publication
Comparative Study
Equivalence Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1916-1925Investigateurs
Charles Marc Samama
(CM)
Nadia Rosencher
(N)
Patrick Mismetti
(P)
Silvy Laporte
(S)
Juan Llau
(J)
Patrick Mouret
(P)
William Fisher
(W)
Michel Cucherat
(M)
Alain Sautet
(A)
Annick Steib
(A)
Philippe Girard
(P)
Francis Couturaud
(F)
Antoine Elias
(A)
Paul Zufferey
(P)
Sandrine Accassat
(S)
Edith Venet
(E)
Emilie Presles
(E)
Gabor Vásárhelyi
(G)
Tibor Laszlo
(T)
Endre Lénárt
(E)
Farid Shafiei
(F)
Gábor Janositz
(G)
István Szabó
(I)
Kálmán Toth
(K)
Tamás Bardos
(T)
Gabor Szabo
(G)
Péter Than
(P)
Jeno Kiss
(J)
David Homer
(D)
Rastislav Ballay
(R)
David Pellar
(D)
Tomas Pink
(T)
Tomas Knybel
(T)
Radek Hart
(R)
Jan Kana
(J)
Jaroslav Altschul
(J)
Tomáš Trc
(T)
Michal Striz
(M)
Martin Repko
(M)
Daniel Duverger
(D)
Serge Molliex
(S)
Emmanuel Samain
(E)
Karim Asehnoune
(K)
Marine Coroir
(M)
Marion Antona
(M)
Claude Girard
(C)
Pierre Albaladejo
(P)
Pierre-Yves Petit
(PY)
Eric Barberichaud
(E)
Bernard Cholley
(B)
Hélène Beloeil
(H)
Xavier Capdevila
(X)
Pierre Diemunsch
(P)
Philippe Cuvillon
(P)
Sigismond Lasocki
(S)
Alexandre Atoui
(A)
François Sztark
(F)
Jean Louis Charissoux
(JL)
Christos Yiannakopoulos
(C)
Konstantinos Kateros
(K)
Spiros Pneumaticos
(S)
John Feroussis
(J)
George A Macheras
(GA)
Ioannis Michos
(I)
Eleftherios Tsiridis
(E)
Konstantinos N Malizos
(KN)
George C Babis
(GC)
Konstantinos Kotsiopoulos
(K)
Vasileios I Sakellariou
(VI)
Antonios Kouzelis
(A)
Stamatios Papadakis
(S)
Perikles Papadopoulos
(P)
Antonios Asimakopoulos
(A)
Sebastian Wysocki
(S)
Jacek Stachowiak
(J)
Julian Dutka
(J)
Tomasz Przymorski
(T)
Grzegorz Kwiatkowski
(G)
Andrzej Reetz
(A)
Jan Skowroñski
(J)
Waldemar Weiss
(W)
Tomasz Trzeciak
(T)
Andrzej Atras
(A)
Marek Pazdzior
(M)
Jerzy Cholewinski
(J)
Szczepan Krupa
(S)
Adel Khorbi
(A)
Lotfi Nouisri
(L)
Mohamed Abdelkefi
(M)
Hassib Keskes
(H)
Ramzi Bouzidi
(R)
Mondher Kooli
(M)
Abderrazek Abid
(A)
Maher Barsaoui
(M)
Javier Martínez Martín
(J)
Enrique Gómez Barrena
(E)
Vicente Molero
(V)
Luis Peidro
(L)
Pere Torner Pifarre
(P)
Victor Rodriguez Vega
(V)
Jesus Campo Loarte
(J)
Carles Morera Domínguez
(C)
Alejandro Braña Vigil
(A)
Manuel Mesa Ramos
(M)
Juan V Llau
(JV)
Leonor Rodríguez
(L)
Andrés Valentí Azcárate
(A)
Luis Javier Roca Ruiz
(LJ)
Vincete Climent Peris
(V)
Luis Alfonso Sanz Ferrando
(LA)
Francisco Chana Rodriguez
(F)
Natalia Medina León
(N)
Claudio Gomez Zubeldia
(C)
Marco Bigoni
(M)
Francesco Franceschi
(F)
Andrea Ferretti
(A)
Andrea Baldini
(A)
Lamberto Felli
(L)
Carlo Trevisan
(C)
Roberto Buda
(R)
Vito Stancanelli
(V)
Maria Cusano
(M)
Mario Tartarone
(M)
Agostino Tucciarone
(A)
Giuseppe Rollo
(G)
Domenico Campanacci
(D)
Aniello De Nicola
(A)
Gianezio Paribelli
(G)
Rocco Romeo
(R)
Astrid Ursula Behr
(AU)
Vincenzo Salini
(V)
Massimo Nolli
(M)
Carlo Doria
(C)
Fabio Rodia
(F)
Mario Bosco
(M)
Antonio Ciardullo
(A)
Arndt Schulz
(A)
Michael Bayer
(M)
Frank Beyer
(F)
Sebastian Illiger
(S)
Richard Stange
(R)
Philipp Drees
(P)
Mark Coburn
(M)
Georg Matziolis
(G)
Yu Kleinlugtenbelt
(Y)
Adel Merah
(A)
Sandrine Ayala
(S)
Commentaires et corrections
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