title: Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Evidence regarding the use of direct oral anticoagulants (DOACs) in the elderly, particularly bleeding risks, is unclear despite the presence of greater comorbidities, polypharmacy, and altered pharmacokinetics in this age group.
  
  
  RESULTS
  We performed a systematic review and meta-analysis of randomized trials of DOACs (dabigatran, apixaban, rivaroxaban, and edoxaban) for efficacy and bleeding outcomes in comparison with vitamin K antagonists (VKA) in elderly participants (aged ≥75 years) treated for acute venous thromboembolism or stroke prevention in atrial fibrillation. Nineteen studies were eligible for inclusion, but only 11 reported data specifically for elderly participants. The efficacy in managing thrombotic risks for each DOAC was similar or superior to VKA in elderly patients. A nonsignificantly higher risk of major bleeding than with VKA was observed with dabigatran 150 mg (odds ratio, 1.18; 95% confidence interval, 0.97-1.44) but not with the 110-mg dose. Significantly higher gastrointestinal bleeding risks with dabigatran 150 mg (1.78, 1.35-2.35) and dabigatran 110 mg (1.40, 1.04-1.90) and lower intracranial bleeding risks than VKA for dabigatran 150 mg (0.43, 0.26-0.72) and dabigatran 110 mg (0.36, 0.22-0.61) were also observed. A significantly lower major bleeding risk in comparison with VKA was observed for apixaban (0.63, 0.51-0.77), edoxaban 60 mg (0.81, 0.67-0.98), and 30 mg (0.46, 0.38-0.57), whereas rivaroxaban showed similar risks.
  
  
  CONCLUSIONS
  DOACs demonstrated at least equal efficacy to VKA in managing thrombotic risks in the elderly, but bleeding patterns were distinct. In particular, dabigatran was associated with a higher risk of gastrointestinal bleeding than VKA. Insufficient published data for apixaban, edoxaban, and rivaroxaban indicate that further work is needed to clarify the bleeding risks of these DOACs in the elderly.
  
  
  BACKGROUND
  http://www.crd.york.ac.uk/PROSPERO. Unique identifier: PROSPERO CRD42014007171/.
authors.affiliation: From Department of Primary Care and Public Health Sciences, King's College London, United Kingdom (M.S., V.R.C., M.M.); Department of Clinical Pharmacy, Guy's and St Thomas Hospital NHS Foundation Trust, London, United Kingdom (M.S.); Department of Haematological Medicine, King's College Hospital, London, United Kingdom (J.P.P.); and Institute of Pharmaceutical Science, King's College London, United Kingdom (J.P.P., J.G.D.). manujsharma2014@gmail.com mariam.molokhia@kcl.ac.uk.
authors.forename: Manuj
authors.initials: M
authors.lastname: Sharma
authors.affiliation: From Department of Primary Care and Public Health Sciences, King's College London, United Kingdom (M.S., V.R.C., M.M.); Department of Clinical Pharmacy, Guy's and St Thomas Hospital NHS Foundation Trust, London, United Kingdom (M.S.); Department of Haematological Medicine, King's College Hospital, London, United Kingdom (J.P.P.); and Institute of Pharmaceutical Science, King's College London, United Kingdom (J.P.P., J.G.D.).
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Cornelius
authors.affiliation: From Department of Primary Care and Public Health Sciences, King's College London, United Kingdom (M.S., V.R.C., M.M.); Department of Clinical Pharmacy, Guy's and St Thomas Hospital NHS Foundation Trust, London, United Kingdom (M.S.); Department of Haematological Medicine, King's College Hospital, London, United Kingdom (J.P.P.); and Institute of Pharmaceutical Science, King's College London, United Kingdom (J.P.P., J.G.D.).
authors.forename: Jignesh P
authors.initials: JP
authors.lastname: Patel
authors.affiliation: From Department of Primary Care and Public Health Sciences, King's College London, United Kingdom (M.S., V.R.C., M.M.); Department of Clinical Pharmacy, Guy's and St Thomas Hospital NHS Foundation Trust, London, United Kingdom (M.S.); Department of Haematological Medicine, King's College Hospital, London, United Kingdom (J.P.P.); and Institute of Pharmaceutical Science, King's College London, United Kingdom (J.P.P., J.G.D.).
authors.forename: J Graham
authors.initials: JG
authors.lastname: Davies
authors.affiliation: From Department of Primary Care and Public Health Sciences, King's College London, United Kingdom (M.S., V.R.C., M.M.); Department of Clinical Pharmacy, Guy's and St Thomas Hospital NHS Foundation Trust, London, United Kingdom (M.S.); Department of Haematological Medicine, King's College Hospital, London, United Kingdom (J.P.P.); and Institute of Pharmaceutical Science, King's College London, United Kingdom (J.P.P., J.G.D.). manujsharma2014@gmail.com mariam.molokhia@kcl.ac.uk.
authors.forename: Mariam
authors.initials: M
authors.lastname: Molokhia
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy*; D006470:Hemorrhage / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D055502:Secondary Prevention / Q000379:methods*; D020521:Stroke / Q000175:diagnosis / Q000517:prevention & control*; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants
keywords: aged; anticoagulants; atrial fibrillation; hemorrhage; meta-analysis; systematic review; venous thromboembolism