Cost-effectiveness Modelling of Novel Oral Anticoagulants Incorporating Real-world Elderly Patients with Atrial Fibrillation

Abstract Background Novel oral anticoagulants (NOACs) expand the treatment options for patients with atrial fibrillation (AF). Their benefits need to be weighed against the risk-benefit ratio in real-world elderly patients, prompting this cost-effectiveness study of NOACs (apixaban, dabigatran, edoxaban and rivaroxaban), warfarin and aspirin for stroke prevention in AF. Methods Applying effectiveness estimates from a network meta-analysis involving over 800,000 patients from randomized controlled trials and observation studies, our Markov model projected cost and health outcomes for a cohort of 65-year-old AF patients over a life-time. We performed subgroup analysis stratified by age (65–74 and ≥ 75years), with further analysis limited to observational studies involving dabigatran and rivaroxaban. Results Compared to warfarin, NOACs (except dabigatran 110) were associated with incremental cost-effectiveness ratios ranging from USD 24,476 to USD 41,448 that were within cost-effectiveness threshold of USD 49,700 (one gross domestic product per capita in Singapore in 2015). Aspirin regimens were dominated. In elderly aged ≥ 75 years, cost effectiveness of NOACs (except apixaban) decreased, owing to worsened performance in safety profile. Analysis limited to observational studies revealed dabigatran 150 and rivaroxaban were not cost-effective, reflecting increased bleeding risks in non-controlled settings. Threshold analyses revealed that apixaban was no longer cost-effective at two to three times higher bleeding risk. Conclusions Whilst NOACs are cost-effective in the younger elderly compared to warfarin, their benefits appear to be offset by worsened risk profile in older elderly, especially in non-controlled settings. Decisions on appropriate AF treatment should balance treatment-related benefits, risks, and patient preference.