The emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke-related non-valvular atrial fibrillation (NVAF). Although several DOACs are available, studies comparing the cost effectiveness of DOACs with vitamin K antagonists for NVAF are scarce. The objective of this study was to assess the cost effectiveness of DOACs and warfarin from the Hong Kong public institutional perspective to inform formulary listing decisions.

A previously developed Markov model was adapted to simulate the lifetime disease progression of a hypothetical cohort of 1,000 patients. Net monetary costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed for the following competing alternatives: warfarin, apixaban (5 mg twice daily), dabigatran 110mg or 150mg (twice daily), and rivaroxaban (20mg once daily). Model inputs were sourced from local real-world evidence, landmark trials, and comprehensive literature reviews. Probabilistic sensitivity analyses and deterministic sensitivity analyses were conducted to address study uncertainties. The willingness-to-pay threshold was set at one times the gross domestic product (GDP) per capita (USD 46,091) per QALY gained.

In base case results, all DOACs provided greater improvements in QALYs at a lower cost than warfarin. Using apixaban as the reference for comparisons among the DOACs, dabigatran 110 mg resulted in greater costs and lower QALY gains and was dominated by apixaban, whereas dabigatran 150 mg provided an incremental QALY of 0.005 at an incremental cost of USD 326, leading to an ICER of USD 67,633 per QALY. The lifetime cost associated with rivaroxaban was lower than for apixaban (-USD 151), but with lower QALY gains (-0.147), resulting in an ICER of USD 1,029 per QALY. In probabilistic sensitivity analysis, the probability of warfarin, rivaroxaban 20 mg, dabigatran 110 mg, dabigatran 150 mg, and apixaban 5 mg being cost effective out of 2,000 iterations was 0 percent, 0 percent, 29.4 percent, 33.2 percent, and 37.4 percent, respectively.

The results indicated that apixaban was the most cost-effective treatment in the management of NVAF, compared with other DOACs and warfarin. This conclusion was consistent under all the uncertainty test scenarios.