title: Clinical and Safety Outcomes of Oral Antithrombotics for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Network Meta-analysis.
abstract: BACKGROUND
  Novel oral anticoagulants (NOACs) expanded the options for stroke prevention in atrial fibrillation (AF). Earlier studies comparing their relative effectiveness and safety typically do not incorporate age-related differences or postmarketing studies. This study aimed to summarize and compare clinical and safety outcomes of oral antithrombotics for stroke prevention in AF in younger (65-74 years) and older (≥75 years) elderly.
  
  
  METHODS
  We searched PubMed, Embase, and The Cochrane Library from inception through May 1, 2015, for randomized and nonrandomized studies comparing NOACs, warfarin, and aspirin in elderly with AF. Stroke and systemic embolism (SSE) and major bleeding (MB) are the main outcomes. We also studied secondary outcomes of ischemic stroke, all-cause mortality, intracranial bleeding, and gastrointestinal bleeding.
  
  
  RESULTS
  Of 5255 publications identified, 25 randomized controlled trials and 24 nonrandomized studies of 897,748 patients were included. NOACs reduced the risk of SSE compared with warfarin (rate ratios [RRs] range from 0.78-0.82). Relative to SSE, NOACs demonstrated a smaller benefit for ischemic stroke (dabigatran 110 mg, RR 1.08; edoxaban, 1.00; apixaban, 0.99). On the contrary, aspirin was associated with a significantly higher risk of SSE, ischemic stroke, and mortality than warfarin or NOACs (RR > 1), particularly in older elderly. Regarding safety, medium-dose aspirin (100-300 mg daily) and aspirin/clopidogrel combination showed an increased risk of MB compared with warfarin (RR 1.17 and 1.15, respectively), as per dabigatran 150 mg and rivaroxaban in older elderly (RR 1.17 and 1.12, respectively). Among the NOACs, dabigatran 150 mg conferred greater gastrointestinal bleeding risk compared with warfarin (RR 1.51), whereas rivaroxaban (RR 0.73) demonstrated less benefit of reduced intracranial bleeding than other NOACs (RRs range 0.39-0.46).
  
  
  CONCLUSIONS
  Lower rates of SSE and intracranial bleeding were observed with the NOACs compared with warfarin. Dabigatran 150 mg and rivaroxaban were associated with higher rates of MB in older elderly.
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore. Electronic address: liang_lin@nhg.com.sg.
authors.forename: Liang
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Geriatric Medicine, Institute of Geriatrics and Active Aging, Tan Tock Seng Hospital, Singapore.
authors.forename: Wee Shiong
authors.initials: WS
authors.lastname: Lim
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: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Ai Leng
authors.initials: AL
authors.lastname: Khoo
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, Institute of Geriatrics and Active Aging, 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: David
authors.initials: D
authors.lastname: Foo
authors.affiliation: Department of Geriatric Medicine, Institute of Geriatrics and Active Aging, Tan Tock Seng Hospital, Singapore.
authors.forename: Jing Jih
authors.initials: JJ
authors.lastname: Chin
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Boon Peng
authors.initials: BP
authors.lastname: Lim
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001281:Atrial Fibrillation; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D020521:Stroke / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents
keywords: Network meta-analysis; antithrombotics; atrial fibrillation; elderly; stroke