title: 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 randomised 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 ≥75years, cost effectiveness of NOACs (except apixaban) decreased, owing to worsened performance in safety profile. Analysis limited to observational studies revealed that 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.
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore. Electronic address: ying_jiao_zhao@nhg.com.sg.
authors.forename: Ying Jiao
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Lin
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Hui Jun
authors.initials: HJ
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Tan Tock Seng Hospital, Singapore.
authors.forename: Keng Teng
authors.initials: KT
authors.lastname: Tan
authors.affiliation: Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore.
authors.forename: Aik Phon
authors.initials: AP
authors.lastname: Chew
authors.affiliation: Department of Cardiology, Tan Tock Seng Hospital, Singapore.
authors.forename: Chee Guan
authors.initials: CG
authors.lastname: Foo
authors.affiliation: Department of Neurology, National Neuroscience Institute, Singapore.
authors.forename: Chia Theng Daniel
authors.initials: CT
authors.lastname: Oh
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Boon Peng
authors.initials: BP
authors.lastname: Lim
authors.affiliation: Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore.
authors.forename: Wee Shiong
authors.initials: WS
authors.lastname: Lim
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000191:economics*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000191:economics*; D003362:Cost-Benefit Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008390:Markov Chains; D064887:Observational Studies as Topic / Q000191:economics; D016032:Randomized Controlled Trials as Topic / Q000191:economics
chemical_list: D000925:Anticoagulants
keywords: Anticoagulant; Atrial fibrillation; Cost-effectiveness analysis; Stroke