OBJECTIVE: To critically review the effectiveness of the novel oral 
anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the 
treatment of acute venous thromboembolism.
DESIGN: Systematic review and random effects meta-analysis. Data were extracted 
independently by two investigators. An adjusted indirect comparison was 
performed to compare between novel oral anticoagulants.
DATA SOURCES: Medline, Embase, and Cochrane Library (from inception to April 
2012). Hand searching of relevant scientific works and contact with experts.
STUDY SELECTION: Randomised controlled trials of novel oral anticoagulants 
compared with vitamin K antagonists for acute venous thromboembolism. Selected 
outcomes were recurrent events, major bleeding, and all cause mortality.
RESULTS: Nine studies met our inclusion criteria, involving 16,701 patients 
evaluated for efficacy and 16,611 for safety. Data were stratified according to 
different novel oral anticoagulants. For recurrent acute venous thromboembolism, 
there were no significant differences in events rates between any of the 
anticoagulants and conventional treatment (rivaroxaban (four studies): relative 
risk 0.85, 95% confidence interval 0.55 to 1.31; dabigatran (two studies): 1.09, 
0.76 to 1.57; ximelagatran (two studies): 1.06, 0.62 to 1.80; and apixaban (one 
study): 0.98, 0.20 to 4.79). Rivaroxaban reduced the risk of major bleeding 
compared with conventional treatment (0.57, 0.39 to 0.84), whereas other novel 
oral anticoagulants did not (0.76 (0.49 to 1.18) for dabigatran; 0.54 (0.28 to 
1.03) for ximelagatran; 2.95 (0.12 to 71.82) for apixaban). For all cause 
mortality there were no significant differences between the novel oral 
anticoagulants and conventional treatment (0.96 (0.72 to 1.27) for rivaroxaban; 
1.00 (0.67 to 1.50) for dabigatran; 0.67 (0.42 to 1.08) for ximelagatran; 6.89 
(0.36 to 132.06) for apixaban). The adjusted indirect comparison between 
rivaroxaban and dabigatran did not show superiority of either drug over the 
others for major bleeding (0.75, 0.41 to 1.34) or the other endpoints.
CONCLUSIONS: Compared with vitamin K antagonists, the novel oral anticoagulants 
had a similar risk of recurrence of acute venous thromboembolism and all cause 
mortality, though rivaroxaban was associated with a reduced risk of bleeding.