OBJECTIVES : Recent availability of real-world data (RWD) of the non-vitamin K oral anticoagulants (NOACs) offers possibilities for the external validation of the previous cost-effectiveness analysis (CEA) findings based on randomized clinical trials (RCTs) results. By including results from both RCTs and RWD into one integrative previously published model, we aimed to evaluate the cost-effectiveness of the NOACs and vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation.

METHODS : The model was updated for the current Dutch setting. The incremental cost-effectiveness ratio was calculated using either efficacy/effectiveness and safety data derived from a network meta-analysis (NMA) synthesizing NOAC RCTs or RWD. We conducted a systematic literature review (SLR) to identify eligible studies to inform the RWD-based analysis.

RESULTS : Multiple RWD studies were identified in the SLR; however, the studies commonly failed to meet the pre-defined eligibility criteria including presenting results for the same endpoints as included in the RCTs and model. Therefore, we used the study that best met the eligibility criteria for the inclusion in the model. In the NMA-based analysis, apixaban appeared to be cost-effective compared to VKA (€3,506 per quality-adjusted life-year) and dominant (cost-saving and more effective) over dabigatran, edoxaban and rivaroxaban. In the RWD-based analysis (external validation), apixaban was dominant over all other anticoagulants.

CONCLUSIONS : Based on RCTs as well as RWD, we conclude that apixaban is generally cost-effective or even cost-saving (less costly and more effective) compared to VKA and other NOACs in the overall population of patients with atrial fibrillation. To validate the results of a RCT-based CEA, RWD should be included in the same model. Yet, this remains a major challenge for many reasons, among which the difference in the assessed endpoints and underlying populations in RCTs and RWD which limits robust comparisons and implementation in CEA models.