title: Concomitant Use of Single Antiplatelet Therapy With Edoxaban or Warfarin in Patients With Atrial Fibrillation: Analysis From the ENGAGE AF-TIMI48 Trial.
abstract: BACKGROUND
  We studied the concomitant use of single antiplatelet therapy (SAPT) on the efficacy and safety of the anti-Xa agent edoxaban in patients with atrial fibrillation (AF).
  
  
  RESULTS
  ENGAGE AF-TIMI 48 was a randomized trial that compared 2 dose regimens of edoxaban with warfarin. We studied both the approved high-dose edoxaban regimen (HDER; 60 mg daily reduced by one half in patients with anticipated increased drug exposure), as well as a lower-dose edoxaban regimen (LDER; 30 mg daily, also reduced by one half in patients with anticipated increased drug regimen). SAPT (aspirin in 92.5%) was administered at the discretion of the treating physician. Cox proportional hazard regressions stratified by SAPT at 3 months with treatment as a covariate were performed. The 4912 patients who received SAPT were more frequently male, with histories of coronary artery disease and diabetes, and had higher CHADS2Vasc and HAS BLED scores than did the 14 977 patients not receiving SAPT. When compared to patients not receiving SAPT, those receiving SAPT had a higher incidence of major bleeding; (adjusted hazard ratio [HRadj]=1.46; 95% CI, 1.27-1.67, P<0.001). SAPT did not alter the relative efficacy of edoxaban compared to warfarin in preventing stroke or systemic embolic events (SEEs): edoxaban versus warfarin without SAPT, hazard ratio (HRadj for HDER)=0.94; (95% CI: 0.77-1.15) with SAPT, HRadj=0.70 (95% CI: 0.50-0.98), P interaction (Pint)=0.14. (HRadj for LDER versus warfarin without SAPT=1.19 (95% CI 0.99-1.43) With SAPT, 1.03 (95% CI, 0.76-1.39) Pint=0.42. Major bleeding was lower with edoxaban than warfarin both without SAPT, HRadj for HDER=0.80 (95% CI, 0.68-0.95), and with SAPT, HRadj=0.82 (95% CI, 0.65-1.03; Pint=0.91). For LDER without SAPT (HRadj=0.56 [95% CI 0.46-0.67]) and with SAPT (HRadj=0.51 [95% CI 0.39-0.66]).
  
  
  CONCLUSIONS
  Patients with AF who were selected by their physicians to receive SAPT in addition to an anticoagulant had a similar risk of stroke/SEE and higher rates of bleeding than those not receiving SAPT. Edoxaban exhibited similar relative efficacy and reduced bleeding compared to warfarin, with or without concomitant SAPT.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00781391.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nordio
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: Indravadan
authors.initials: I
authors.lastname: Patel
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: Minggao
authors.initials: M
authors.lastname: Shi
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: Michele
authors.initials: M
authors.lastname: Mercuri
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA ebraunwald@partners.org.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban
keywords: anticoagulant; antiplatelet; atrial fibrillation; edoxaban