SLR - July 2020 - Logan H. Mitchell
Reference: 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. Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery. N Engl J Med 2020 March;382:1916-25.Scientific Literature Review
Reviewed By: Logan H. Mitchell, DPM
Residency Program: Kaiser SF Bay Area Foot & Ankle – Oakland, CA
Podiatric Relevance: Deep venous thrombosis (DVT) after lower extremity orthopaedic surgery can be a disastrous complication, leading to long term complications, disability, and in severe cases, death. There is an overall lack of consensus regarding the use of postoperative thromboprophylaxis. Commonly used medications are aspirin, enoxaparin, and more recently, direct oral anticoagulants. Direct oral anticoagulants (DOAC’s)(e.g. rivaroxaban) are an appealing option. These oral medications do not require close laboratory monitoring and provide simple administration. However, there is little research elucidating their role in DVT prophylaxis, thus this study may help guide a surgeon in choosing an appropriate agent for postoperative thromboprophylaxis.
Methods: This was an international, parallel-group, randomized, double-blind, trial sponsored by Bayer Pharmaceuticals. Eligible patients included adults undergoing non major lower extremity surgery who received thromboprophylaxis for at least two weeks. Surgeries included all lower extremity surgery except: Femoral neck fractures, femoral head fractures, and total knee arthroplasty. Post-operatively, patients were randomized into two groups. The enoxaparin group (n=1640) received enoxaparin 40 mg subcutaneous daily and an oral placebo. The rivaroxaban group (n=1661) received rivaroxaban 10 mg daily and a placebo subcutaneous injection. All patients underwent post treatment ultrasonography to evaluate for DVT and had a telephone visit evaluating outcome measures. Patients that discontinued treatment early were excluded. The primary outcome measure was having a symptomatic DVT, pulmonary embolism (PE), or venous thromboembolic event-related death. Secondary outcomes were: major or minor bleeding events, overt thrombocytopenia or death from any cause.
Results: There were no differences in number of unused doses between groups or in duration of treatment. There was a statistically significant lower incidence of symptomatic DVT, PE, and venous thromboembolic related death in the rivaroxaban group compared to the enoxaparin group (0.2 percent vs. 1.1 percent). The average time to a thromboembolic event was 26 days postoperatively. There was no significant difference between groups in regard to major or minor bleeding events (1.0 percent vs. 1.1 percent). Additionally, no significant difference was found between groups regarding death from any cause or thrombocytopenia.
Conclusions: This paper effectively adds literature to an area that has not been well studied. The authors conclude that oral rivaroxaban is superior to enoxaparin in reducing the occurrence of DVT in non-major lower extremity orthopaedic surgery, without a difference in bleeding risk. The limitations of this study were an overall young and healthy patient population, no true placebo group, and only two comparison groups. Additionally, although enoxaparin is used in DVT prophylaxis in lower extremity surgery, there are more common medications for this in the United States, such as aspirin. Overall, this study is a very well designed and a high powered study for evaluating a highly debated topic in foot and ankle surgery. It provides evidence for using DOAC’s for DVT prophylaxis in lower extremity surgery.