title: Evaluation of Dose-Reduced Direct Oral Anticoagulant Therapy.
abstract: BACKGROUND
  Compared with vitamin K antagonists, direct-acting oral anticoagulants (DOACs) have fixed dosing, limited drug interactions, and do not require therapeutic drug level monitoring. Dose adjustments are recommended for moderate renal dysfunction, low body weight, and select drug interactions.
  
  
  OBJECTIVE
  The aim of our study is to determine if DOAC dose reductions were appropriate based on the manufacturer labeling recommendations for each agent. We also followed patients' treatment outcomes.
  
  
  METHODS
  We retrospectively reviewed patients administered a DOAC at a reduced dose between January 2011 and August 2014. The primary outcome was adherence to current manufacturer dose recommendations. The secondary outcome measures were the incidence of thromboembolic events or any bleeding episodes, regardless of severity, while on therapy.
  
  
  RESULTS
  Of 224 patients included in the analysis, 43.3% of patients fit criteria for a dose adjustment according to manufacturer recommendations. Only 3 of 28 (10.7%) patients treated with apixaban met 2 out of 3 clinical criteria required for a dose reduction per manufacturer recommendations. Only 54.7% of rivaroxaban-treated patients and 32.2% of dabigatran-treated patients had renal insufficiency requiring a dose reduction. Half of our patient population received aspirin therapy, with 6.3% of patients on triple antithrombotic therapy (dual antiplatelet agents plus an anticoagulant). A past medical history significant for bleeding was prevalent in patients treated with a reduced-dose DOAC (32.1%, 20.4%, and 25.4% of patients in the apixaban-, rivaroxaban-, and dabigatran-treated groups, respectively). Thromboembolic events occurred in 10.7%, 3.6%, and 5.1% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively. Frequency of bleeding complications, regardless of severity, was 17.9%, 18.2%, and 23.7% of patients in the apixaban, rivaroxaban, and dabigatran groups, respectively.
  
  
  CONCLUSIONS
  We found that dose-adjusted DOAC therapy was often prescribed in a dose that was lower than package insert recommendations.
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Barra
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: John
authors.initials: J
authors.lastname: Fanikos
authors.affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Connors
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Katelyn W
authors.initials: KW
authors.lastname: Sylvester
authors.affiliation: Thrombosis Research Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Gregory
authors.initials: G
authors.lastname: Piazza
authors.affiliation: Thrombosis Research Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: sgoldhaber@partners.org.
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage; D001241:Aspirin / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D015897:Comorbidity; D003404:Creatinine / Q000097:blood; D000069604:Dabigatran / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000008:administration & dosage*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000008:administration & dosage*; D011728:Pyridones / Q000008:administration & dosage*; D051437:Renal Insufficiency / Q000097:blood / Q000453:epidemiology; D012189:Retrospective Studies; D000069552:Rivaroxaban / Q000008:administration & dosage*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D054556:Venous Thromboembolism / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D000991:Antithrombins; D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban; D003404:Creatinine; D000069604:Dabigatran; D001241:Aspirin
keywords: Anticoagulation; Atrial fibrillation; Dose reduction; Drug interactions; Renal dysfunction; Venous thromboembolism