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Abstract
Objectives To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs).
Design Systematic review and meta-analysis.
Setting We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019.
Participants Patients with AF.
Main outcome measures The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I2 statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist.
Results A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I2=59.9%), $6353.24 ($4076.03 to $8630.45; I2=0%), $7664.58 ($2979.79 to $12 349.37; I2=0%) and $8573.07 ($1877.05 to $15 269.09; I2=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I2=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs.
Conclusions Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP.
PROSPERO registeration number CRD 42019146610.
- health care economics and organizations
- economics
Data availability statement
No data are available. The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.
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Data availability statement
No data are available. The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.
Supplementary materials
Supplementary Data
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Footnotes
Contributors RN, BSB, SY and AT conceived and designed the work. RN and BSB did the analysis. RN wrote the first draft of the manuscript with input from SY and AT. All authors interpreted the data, provided critical revision for important intellectual content and approved the final version to be published.
Funding This work was supported by funding from Mahidol University and the International Decision Support Initiative (iDSI) through the doctoral study in Mahidol University Health Technology Assessment (MUHTA) Graduate Programme. This work was produced as part of the iDSI (www.idsihealth.org), which supports countries to get the best value for money from health spending. iDSI receives funding support from the Bill & Melinda Gates Foundation and the UK Department for International Development.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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