title: Management of Major Bleeding in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice (from Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]).
abstract: Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement.
authors.affiliation: Division of Cardiovascular Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah; Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina. Electronic address: benjamin.steinberg@hsc.utah.edu.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Steinberg
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: DaJuanicia N
authors.initials: DN
authors.lastname: Simon
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Hofstra Northwell School of Medicine, New York, New York.
authors.forename: Jack
authors.initials: J
authors.lastname: Ansell
authors.affiliation: Division of Cardiology, University of California Los Angeles, Los Angeles, California.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, Pennsylvania.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kowey
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D016913:Blood Component Transfusion / Q000379:methods*; D019468:Disease Management; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology / Q000628:therapy*; D006489:Hemostatic Techniques; D006801:Humans; D015994:Incidence; D008297:Male; D011379:Prognosis; D012042:Registries; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014812:Vitamin K; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin