Page 2 - Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery

The new engl and jour nal of medicine

he risk of venous thromboembolism rivaroxaban with enoxaparin in patients under-
— encompassing deep-vein thrombosis and going nonmajor orthopedic surgery in a lower
Tpulmonary embolism — after major or- limb. The trial was sponsored by Centre Hospit-
thopedic surgery is high and is associated with alier Universitaire de Saint-Etienne, France, and
long-term complications, functional disability, and by Bayer. The protocol (including the statistical
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death. Clinical guidelines therefore recommend analysis plan), available with the full text of this
anticoagulant thromboprophylaxis after total hip article at NEJM.org, was developed by the au-
or knee replacement or hip-fracture surgery to thors and approved by the relevant regulatory
reduce the risk of a thrombotic event. 2 authorities and ethics committees. The steering
Nonmajor orthopedic surgery of the lower committee had overall scientific responsibility
limbs (i.e., excluding total hip or knee replacement for the trial, which was managed by the contract
or hip-fracture surgery) that results in transient research organization PSNResearch. An inde-
reduced mobility also involves a risk of major pendent data and safety monitoring committee
venous thromboembolism of approximately 3% monitored the safety and efficacy data. Analyses
without prophylaxis in patients who have a distal were performed independently by the academic
lower-limb injury or undergo knee arthroscopy. statistician. Bayer had no role in the design or
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This risk increases with patient-related risk factors, conduct of the trial; the collection, management,
including coexisting medical conditions, age, obe- analysis, or interpretation of the data; the prepa-
sity, previous venous thromboembolism, medica- ration or approval of the manuscript; or the deci-
tions, pregnancy or the postpartum state, and sion to submit the manuscript for publication.
procoagulant changes after surgery. 4,5 Medical writing assistance was funded by Centre
There is a lack of consensus on the use of Hospitalier Universitaire de Saint-Etienne. The
thromboprophylaxis in patients undergoing non- authors vouch for the completeness and accuracy
major orthopedic surgery. In the United States, of the data and for the fidelity of the trial to the
routine mechanical (nonpharmacologic) or phar- protocol.
macologic prophylaxis is not required because
U.S. guidelines assert that the risk of venous Trial Population
thromboembolism after such surgery is low. Euro- Adults who had been admitted to the hospital to
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pean guidelines, however, recommend a person- undergo nonmajor orthopedic surgery in the
alized strategy of prophylaxis with low-molecular- lower limbs and were to receive thromboprophy-
weight heparin in patients who have one or more laxis for at least 2 weeks (according to the investi-
risk factors and whose risk of a thrombotic event gator’s assessment of the patient’s venous throm-
exceeds that of a bleeding event. 4,7,8 Consequent- boembolic risk) were eligible for enrollment in the
ly, thromboprophylaxis after nonmajor orthope- trial. Types of surgery included Achilles’ tendon
dic surgery remains a standard of care in many repair; knee surgery (including unicompartmen-
European countries. tal knee prosthesis); surgery involving the tibial
As compared with enoxaparin therapy, treat- plateau or femur (excluding femoral head or neck
ment with the factor Xa inhibitor rivaroxaban re- fractures); tibial or ankle fractures or tibial oste-
sults in a lower risk of a composite of symptom- otomy; tibial tuberosity transposition; arthrode-
atic venous thromboembolism and death from any sis of the knee, ankle, or hindfoot; ligament re-
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cause after elective total knee or hip replacement pair of the knee with a planned immobilization
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and is indicated in those contexts. We conducted or partial weight bearing; ligament repair of the
the Prophylaxis in Nonmajor Orthopaedic Sur- ankle; or any elective orthopedic lower-limb sur-
gery (PRONOMOS) trial to compare the effect of gery necessitating the use of thromboprophylaxis
rivaroxaban with that of enoxaparin in the pre- for more than 2 weeks. The enrollment criteria are
vention of major venous thromboembolism after described in the Supplementary Appendix, avail-
lower-limb nonmajor orthopedic surgery. able at NEJM.org. All the participants provided
written informed consent.
Methods
Procedures
Trial Design Prerandomization treatment with low-molecular-
In this international, parallel-group, randomized, weight heparin was allowed for a maximum of
double-blind, noninferiority trial, we compared 48 hours before surgery (maximum of one dose
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