Page 1 - Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery

The new engl and jour nal of medicine

Original Article

Rivaroxaban or Enoxaparin
in Nonmajor Orthopedic Surgery

C. Marc Samama, M.D., Silvy Laporte, Ph.D., Nadia Rosencher, M.D.,
Philippe Girard, M.D., Juan Llau, M.D., Patrick Mouret, M.D.,
William Fisher, M.D., Javier Martínez-Martín, M.D, Daniel Duverger, M.D.,
Béatrice Deygas, M.Sc., Emilie Presles, M.Sc., Michel Cucherat, M.D.,
and Patrick Mismetti, M.D., for the PRONOMOS Investigators*

ABSTR ACT

BACKGROUND
Nonmajor orthopedic surgery of the lower limbs that results in transient reduced The authors' affiliations are listed in the
mobility places patients at risk for venous thromboembolism. Rivaroxaban may be Appendix. Address reprint requests to
noninferior to enoxaparin with regard to the prevention of major venous thrombo- Dr. Samama at Groupe Hospitalo-Univer-
sitaire AP-HP Centre–Université de Paris,
embolism in these patients. Hôpital Cochin, Service d’Anesthésie–
Réanimation, 27 rue du Faubourg St.
METHODS Jacques, 75014 Paris, France, or at marc
In this international, parallel-group, randomized, double-blind, noninferiority trial, . samama@ aphp . fr.
we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic *A complete list of the PRONOMOS inves-
surgery who were considered to be at risk for venous thromboembolism on the tigators is provided in the Supplemen-
basis of the investigator’s judgment to receive either rivaroxaban or enoxaparin. The tary Appendix, available at NEJM.org.
primary efficacy outcome of major venous thromboembolism was a composite of This article was published on March 29,
symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or 2020, at NEJM.org.
venous thromboembolism–related death during the treatment period or asymptom- DOI: 10.1056/NEJMoa1913808
atic proximal deep-vein thrombosis at the end of treatment. A test for superiority Copyright © 2020 Massachusetts Medical Society.
was planned if rivaroxaban proved to be noninferior to enoxaparin. For all out-
comes, 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 rel-
evant bleeding.
RESULTS
A total of 3604 patients underwent randomization; 1809 patients were assigned to
receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembo-
lism 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 ortho-
pedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de
Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.)

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