The Effectiveness and Safety of Direct Oral Anticoagulants Following Lower Limb Fracture Surgery: A Systematic Review and Meta-analysis

Objectives: Venous thromboembolism (VTE) is a well-established complication after many orthopaedic injuries, such as hip and lower limb fractures. The use of direct oral anticoagulants (DOACs, previously termed novel oral anticoagulants) is well-established as thromboprophylaxis after major elective orthopaedic surgery, but not in the nonelective setting. The aim of this study was to investigate the effectiveness and safety of DOACs after nonelective lower limb fracture surgery. Data Sources: A systematic literature search of the MEDLINE, EMBASE, CINAHL, and CENTRAL databases was conducted. No limitation was placed on publication date, with only manuscripts printed in English were eligible. Study Selection: Included studies were either randomized controlled trials or prospective and retrospective comparative studies. Included studies compared DOACs to conventional methods of thromboprophylaxis in the postoperative period after surgical management of lower limb fractures. Data Extraction: Outcomes included VTE, bleeding, wound complications, mortality, and adverse events. Eight studies met inclusion criteria, of which 7 compared direct factor Xa inhibitors (XaIs) with conventional VTE prophylaxis and one study compared a direct thrombin inhibitor with conventional VTE prophylaxis. Data Synthesis: Revman 5.3 (Nordic Cochrane Centre, Denmark) was used to complete the meta-analysis and generate forest plots. Conclusions: XaIs were shown to have lower rates of deep vein thrombosis (Odds ratio 0.59; 95% confidence interval, 0.46-0.76; P < 0.0001) and less pharmacologically attributable adverse events (Odds ratio 0.62; 95% confidence interval, 0.46-0.82; P = 0.0007). There was difference between DOACs and conventional VTE prophylaxis regarding mortality, PE, symptomatic deep vein thrombosis, or bleeding events. The results generally support the use of DOACs for VTE prophylaxis after nonelective lower limb fracture surgery, such after hip fracture. The results more strongly support the use of XaIs; however, more evidence is needed to fully assess DOACs' role in clinical practice.