Systematic review of randomized controlled trials of new anticoagulants for venous thromboembolism prophylaxis in major orthopedic surgeries, compared with enoxaparin.
BACKGROUND
In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis.


OBJECTIVE
To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery.


METHODS
A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators.


RESULTS
Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin.


CONCLUSIONS
NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice.
Department of Surgery and Orthopedics, Botucatu School of Medicine, Paulista State University, Botucatu, São Paulo, Brazil. : ricardoyoshida@gmail.com
Ricardo de Alvarenga
Rde A
Yoshida
Winston Bonetti
WB
Yoshida
Francisco Humberto de Abreu
FH
Maffei
Regina
R
El Dib
Rogério
R
Nunes
Hamilton Almeida
HA
Rollo
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D017558:Elective Surgical Procedures; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D019637:Orthopedic Procedures / Q000009:adverse effects*; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin