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

Abstract

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. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

New Oral Anticoagulants for Venous Thromboembolism Prophylaxis in Total Hip and Knee Arthroplasty: A Systematic Review and Network Meta-Analysis

“…Up to now, several systematic reviews and meta-analyses have been conducted to assess the effectiveness and safety risk of NOACs. Compared with conventional VTE prophylaxis, NOACs was also strongly supported to use in nonelective lower limb fracture surgery, such as after hip fracture ( Waever et al, 2021 ). Similar to our study, Rezapour et al confirmed that rivaroxaban was also shown to be more cost-effective than apixaban and dabigatran in the prevention of VTE after total knee and total hip replacement surgery ( Rezapour et al, 2021 ).…”

Recommendations from the ICM-VTE: Trauma

“…ASA and DOAC use have come under investigation of late. Two heterogenous meta-analyses, recently published, suggest favorable findings with regards to VTE reduction, however level one evidence is yet to emerge 268,269 . Both agents are convenient given their more simplistic oral regimens and encouragingly low rates of VTE, but reservations persist concerning hemorrhagic events, particularly in the immediate postoperative period 263,270 .…”

“…Rationale: Venous thromboembolism (VTE) is a significant source of morbidity and mortality following orthopedic surgery 153,154 . The risk of VTE following orthopaedic surgery varies significantly based on many patient and surgical factors 155-159 . It is important to stratify this risk in order to develop an appropriate anticoagulation plan post-operatively 160-162 .…”

Direct oral anticoagulants for venous thromboembolism prophylaxis in orthopaedic trauma: a clear first choice?

“…12 Studies from the last decade have consistently demonstrated the benefits of DOACs over LMWH for VTEp in orthopaedic trauma surgery. 13,14 A recent systematic review and meta-analysis reported significantly reduced deep venous thrombosis rates when Factor Xa inhibiting DOACs were compared to LMWH for VTEp after lower limb fracture surgery. 14 DOACs were also not inferior to LMWH for prevention of mortality, pulmonary embolism and bleeding, both major and minor.…”

“…13,14 A recent systematic review and meta-analysis reported significantly reduced deep venous thrombosis rates when Factor Xa inhibiting DOACs were compared to LMWH for VTEp after lower limb fracture surgery. 14 DOACs were also not inferior to LMWH for prevention of mortality, pulmonary embolism and bleeding, both major and minor. A RCT not included in the aforementioned study demonstrated reduced VTE risk with no increase bleeding risk, including minor bleeding, when rivaroxaban was compared to LMWH.…”