OBJECTIVES: Direct oral anticoagulants (DOACs) are now used to prevent venous thromboembolism (VTE) following total knee and hip replacements (TKR and THR). This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using DOACs for the prevention of VTE in a population undergoing TKR or THR surgeries.

METHODS: We performed a comprehensive search in several databases published before June 2021. Studies were included if they were cost-effectiveness analysis reporting cost per quality-adjusted life year (QALY) or life year (LY) of DOACs compared to low molecular-weight heparins (LMWHs) or other agents for the prevention of VTE after TKR or THR. Risk of bias was assessed using the biases in economic studies (ECOBIAS) checklist. Various monetary units were converted to purchasing power parity, adjusted to 2020 US dollars. The INBs were calculated and then pooled across studies, stratified by country income level (i.e., high-income countries (HICs) and low- and middle-income countries (LMICs)), using a random-effects model. Heterogeneity was assessed using the I2 statistic.

RESULTS: A total of 47 comparisons (24 for TKR and 23 for THR) from 16 studies was included. In HICs, DOACs were cost-effective for the prevention of VTE after both TKR and THR with corresponding INBs (95% CI; I²) of $221.22 ($143.18, $299.27; 20.42%) and $252.95 ($164.49, $341.42; 47.87%) compared to LMWHs or warfarin, respectively. In LMICs, DOACs were not cost-effective for both TKR and THR with the INBs of $38.85 (-$21.62, $99.32; 6.97%) and $64.73 (-$116.81, $246.26; 82.79%) compared to LMWHs, respectively. No evidence of small-study effects was identified in any analyses. The cost-effectiveness of using DOACs for TKR and THR in HICs was robust across a series of sensitivity analyses.

CONCLUSIONS: DOACs were cost-effective as compared to LMWHs for VTE prophylaxis following TKR and THR surgeries in HICs. Further studies from LMICs are warranted.