Objective: To evaluate cost differences between stroke/systemic embolism (S/SE) and major bleeding (MB) among nonvalvular atrial fibrillation (NVAF) patients with multimorbidity prescribed direct oral anticoagulants (DOACs) or warfarin.

Methods: Using CMS Medicare data, a retrospective observational study of age 65+ NVAF patients with multimorbidity (having ≥6 comorbidities) initiating apixaban, dabigatran, rivaroxaban, or warfarin from 01JAN2012-31DEC2017 was conducted. Cohorts were matched utilizing propensity score matching (PSM). All-cause healthcare costs were estimated by generalized linear models and two-part models with bootstrapping were used to estimate S/SE- and MB-related medical costs. Costs were calculated per patient per month.

Results: After PSM, 74,481 apixaban-warfarin, 12,458 dabigatran-warfarin, 59,305 rivaroxaban-warfarin, 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban matched pairs with 8-9 months mean follow-up were included. Cohorts were balanced with mean ages of 78-80 years and mean CHA2DS2-VASc score of 5.7-5.9. Compared to warfarin, apixaban patients incurred lower all-cause ($4,471 vs. $4,967, P<0.001), S/SE ($71 vs. $106, P=0.026) and MB ($213 vs. $358, P<0.001) costs; dabigatran patients incurred lower all-cause ($4,248 vs. $4,766, P<0.001), S/SE ($64 vs. $104, P=0.047) and MB ($235 vs. $330, P=0.004) costs; and rivaroxaban patients incurred lower all-cause ($4,536 vs. $4,833, P<0.001), S/SE ($70 vs. $103, P=0.001) and MB ($307 vs. $341, P=0.035) costs. Compared to rivaroxaban, apixaban patients incurred lower all-cause ($4,313 vs. $4,488, P=0.002) and MB ($209 vs. $306, P<0.001) costs, and similar S/SE ($70 vs. $69, P=0.973) costs. Dabigatran (vs. rivaroxaban) patients incurred lower MB ($240 vs. $294, P=0.049) costs and similar all-cause ($4,244 vs. $4,419, P=0.145) and S/SE ($64 vs. $74, P=0.447) costs. Apixaban (vs. dabigatran) patients incurred similar all-cause ($4,248 vs. $4,245, P=0.975), S/SE ($55 vs. $64, P=0.512), and MB ($192 vs. $241, P=0.089) costs.

Conclusion: NVAF patients with multimorbidity incurred varying all-cause, S/SE and MB costs when comparing DOACs to warfarin and DOACs to DOACs.