Network Meta-Analysis to Estimate Treatment Efficacy: The Example of Venous Thromboembolism Prophylaxis Strategies in Major Orthopaedic Surgeries

Aim
To review and synthesise the evidence from randomised controlled trials (RCTs) which assessed the efficacy of venous thromboembolism (VTE) prophylaxis strategies in people undergoing major orthopaedic surgeries using network met-analysis (NMA).
Methods
Systematic reviews of randomised controlled trials (RCTs) assessing the efficacy of VTE prophylaxis in elective total hip replacement (eTHR) and elective total knee replacement (eTKR) were undertaken. The following databases were searched: The Cochrane Library (CENTRAL), EMBASE and Medline. Risk of bias was assessed using The Cochrane risk-of-bias tool. Bayesian NMAs of three outcomes (deep vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding (MB)), for each population, were undertaken using the software WinBugs 1.4.3. The median (95% credible intervals (CrIs)) relative risk (RR) and odds ratio (OR) compared to no prophylaxis, ranks and probability of being the best were calculated.
Results
For eTKR, rivaroxaban for 14 days had the highest probability of being the most effective in terms of DVT prevention (RR=0.12, 95% CrI: 0.09 to 0.56). Low-molecular-weight-heparin (LMWH) at a standard prophylactic dose (40mg once daily) for 28-35 days ranked first in the pulmonary embolism (PE) network (RR = 0.02 [0.00 to 3.86]). LMWH at a low prophylactic dose for 14 days ranked first in the MB network (OR = 0.52 [0.08 to 2.89]).
For eTHR, rivaroxaban for 28-35 days (RR = 0.06, 95% credible interval (CrI): 0.01 to 0.29) had the highest probability of being best in the DVT network. A strategy of LMWH at a standard prophylactic dose for 10 days followed by low-dose aspirin for 28 days had the highest probability of being best in the PE (RR= 0.0011 [0.00 -0.096]) and MB (OR = 0.37 [0.00-26.96]) networks respectively.
The PE and MB networks’ results were highly uncertain; with very wide CrIs around the median estimates for both eTHR and eTKR.
Conclusion
Pharmacological prophylaxis strategies are more effective compared to mechanical methods in the prevention of DVT, with rivaroxaban ranked higher compared to other strategies. However, this comes at the expense of a possible increase in major bleeding. An outcome measure that reflects the impact of both VTE and bleeding, for example quality of life, would be more appropriate for guiding clinicians’ decisions regarding the choice of the optimal VTE prophylaxis strategy.
Disclaimer:
This work was undertaken by the National Guideline Centre (NGC), Royal College of Physicians London which received funding from the National Institute for Health and Care Excellence (NICE). The views expressed in this publication are those of the authors and not necessarily those of the Institute.