Oral anticoagulants/LMW heparins provide comparable safety in antithrombotic prophylaxis

Study Type: Meta-analysis/Systematic Review
OE Level of Evidence: 1
Journal Level of Evidence: N/A
25 randomized controlled trials (RCTs) investigating the safety of direct oral anticoagulants and low molecular weight heparin/fondaparinux in antithrombotic prophylaxis during total hip replacement, total knee replacement, and hip fracture surgery were included. This meta-analysis was conducted in order to determine if direct oral anticoagulants, in addition to the more convenient oral administration and potentially increased compliance rates, are able to provide an enhanced safety profile. The findings of Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Non-funded
Conflicts: Other
Why was this study needed now?
One of the most commonly encountered complications in orthopaedic surgery is venous thromboembolism (VTE), including both deep vein thrombosis (DVT) and pulmonary embolism (PE). The current standard for antithrombotic prophylaxis in major orthopaedic surgery is the daily subcutaneous injection of low molecular weight heparins (LMWHs), however, this method of antithrombotic prophylaxis can be cumbersome and has been associated with a low, but not insignificant, risk of heparin-induced thrombocytopenia. The use of numerous direct oral anticoagulants (DOACs) as an alternative for antithrombotic prophylaxis has become more frequent due to the ease of administration and resulting increase in post-discharge medication compliance. Although previous analyses have evaluated these treatment interventions, none have compared the consequences that arise from postsurgical major bleeding that occurs during the thromboprophylaxis, thus warranting the present meta-analysis.
What was the principal research question?
How do the rates of fatal bleeding and the case fatality rates of major bleeding compare between low molecular weight heparins (LMWH)/fondaparinux and direct oral anticoagulants (DOACS) when used as antithrombotic prophylaxis in major orthopaedic surgery?
Data Source: An online search of MEDLINE and EMBASE was performed to identify literature published from database inception to March 2015. Abstract books from the Congresses of the International Society on Thrombosis and Haemostasis, European Society of Cardiology, Mediterranean League Against Thromboembolic Diseases, American Heart Association, American Society of Hematology, American College of Cardiology, American Academy of Orthopaedic Surgeons, Orthopaedic Research Society, and European Orthopaedic Research Society were reviewed between 2004 and 2015 to identify unpublished studies. A manual search of the reference lists of retrieved articles was also conducted, as were searches of ClinicalTrials.gov and the websites of pharmaceutical companies in order to identify any gray literature.
Index Terms: The search strategy can be found in the supplementary table in the online version of the study.
Study Selection: Two authors independently reviewed the literature identified from the systematic search and selected articles for inclusion if they were phase II or III randomized controlled trials, with patients undergoing major orthopaedic surgery (total hip or knee replacement, or hip fracture surgery) without restrictions based on language. Additional inclusion criteria included: an intervention group receiving one of the novel direct oral anticoagulants (DOACs); a comparator group receiving low molecular weight heparins (LMWHs) /fondaparinux; and major, fatal, and intracranial bleeding as measured outcomes. Any disagreements between the reviewers were resolved through discussion and if consensus was still not reached, a third author was consulted. A total of 25 RCTs (42170 patients) were included.
Data Extraction: Data was extracted by two independent authors. Authors of the original studies were contacted if data was insufficient.
Data Synthesis: Review Manager Software (version 5.1), Comprehensive meta-analysis software (version 2) and StatsDirect Statistical Software (version 2.8.0) were used to perform statistical analyses. Major and fatal bleeding, along with intracranial hemorrhage, were expressed using relative risk (RR) with 95% confidence intervals (CI) and using weighted mean incidence rates. Absolute risk reduction (ARR) and absolute risk increase (ARI) with the corresponding number needed to treat (NNT) and number needed to harm (NNH) were calculated for each treatment. The case-fatality rate of major bleeding was reported as a percentage and as a weighted mean rate. Both random- and fixed- effects models were used to pool data, and p<0.05 was indicative of a significant difference. Heterogeneity was assessed using the Cochrane Q statistic & the I2 statistic, and a funnel plot was used to assess publication bias. Sensitivity analyses were performed with only high-quality literature and European Medicines Agency approved dose regiments. Subgroup analyses were performed based on surgical procedure, DOAC type, enoxaparin regimen used, study population, and study design.
What were the important findings?
What should I remember most?
How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.